Materiały źródłowe

• #1 Radiation Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441931/

  Prolonged or significant exposure to ionizing radiation can result in acute radiation syndrome. The National Council on Radiation Protection and Measurements defines this as „a broad term used to describe a range of signs and symptoms that reflect severe damage to specific organ systems and that can lead to death within hours or up to several months after exposure.” […] Acute radiation syndrome can result from direct exposure or contamination by radioactive materials. Direct exposure can be caused by a nuclear blast, while contamination can result from the ingestion of nuclear-contaminated food, water, and skin contact with the nuclear material. Acute radiation syndrome is divided into 3 groups: hematopoietic, gastrointestinal, and cardiac/neurological systems. Each system will require a different dose of radiation to manifest the symptoms of acute radiation syndrome. The timing of symptoms is also subdivided into prodrome, latent, and manifest phases. […] Radiation is detrimental to body tissues based on how quickly their cells turn over. Those with a high mitotic index will be more severely affected at a lower dose. These include bone marrow, the gastrointestinal tract, and skin.

• #2 Acute radiation syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Acute_radiation_syndrome

  Acute radiation syndrome (ARS), also known as radiation sickness or radiation poisoning, is a collection of health effects that are caused by being exposed to high amounts of ionizing radiation in a short period of time. […] ARS involves a total dose of greater than 0.7 Gy (70 rad), that generally occurs from a source outside the body, delivered within a few minutes. […] At high doses, this causes DNA damage that may be irreparable. […] Exposure to high doses of radiation causes DNA damage, later creating serious and even lethal chromosomal aberrations if left unrepaired. […] Ionizing radiation can produce reactive oxygen species, and does directly damage cells by causing localized ionization events. […] Clustered damage takes longer to repair than isolated breakages, and is less likely to be repaired at all. […] Larger radiation doses are more prone to cause tighter clustering of damage, and closely localized damage is increasingly less likely to be repaired.

• #3 Radiation sickness – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/radiation-sickness/symptoms-causes/syc-20377058

  Radiation sickness is damage to the body caused by a large dose of radiation often received over a short time. This is called acute radiation sickness. […] Radiation sickness is caused by being exposed to a high dose of radiation. Radiation is the energy released from atoms as either a wave or a tiny particle of matter. […] Radiation sickness happens when high-energy radiation damages or destroys certain cells in the body. Areas of the body most at risk of being affected by high-energy radiation are the bone marrow cells and the lining of the intestinal tract.

• #4 Acute radiation syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Acute_radiation_syndrome

  Acute radiation syndrome (ARS), also known as radiation sickness or radiation poisoning, is a collection of health effects that are caused by being exposed to high amounts of ionizing radiation in a short period of time. […] ARS involves a total dose of greater than 0.7 Gy (70 rad), that generally occurs from a source outside the body, delivered within a few minutes. […] At high doses, this causes DNA damage that may be irreparable. […] Exposure to high doses of radiation causes DNA damage, later creating serious and even lethal chromosomal aberrations if left unrepaired. […] Ionizing radiation can produce reactive oxygen species, and does directly damage cells by causing localized ionization events. […] Clustered damage takes longer to repair than isolated breakages, and is less likely to be repaired at all. […] Larger radiation doses are more prone to cause tighter clustering of damage, and closely localized damage is increasingly less likely to be repaired.

• #5 CBRNE – Radiation Emergencies: Overview, Terminology, Biologic Effects of Ionizing Radiation

  https://emedicine.medscape.com/article/834015-reference

  The principal pathologic effect of ionizing radiation results from damage to DNA. Regardless of the form of ionizing radiation, the common pathway of injury is that the radiation deposits a relatively large amount of energy into the electron orbitals of atoms in the biologic medium. This energy transfer raises the energy level (excites) of the electron and, if sufficient, ejects the electron from the atom, resulting in a now positively charged atom (ionization). […] These charged particles are chemically active, resulting in breakage of the chemical bonds within the DNA molecule. In addition to this direct injury, ionization radiation interacts with cellular water, forming free radicals, which can also damage the chemical bonds in the DNA strands. Regardless of the form of ionizing radiation (alpha, beta, gamma, x-ray, neutrons) or whether the damage is direct or indirect via free radical formation, the final pathologic injury is disruption of chemical bonds in the DNA strands. DNA damage is dose dependant, with the most common damage being single-strand breaks. As long as the number of breaks is not overwhelming and the complementary DNA template remains intact, these injuries are repaired with little biological consequence. In contrast, if the injury results in a double-strand break, the repair template is lost and can result in cell death, mutations, or carcinogenesis.

• #6 Clinical manifestations, evaluation, and diagnosis of acute radiation exposure – UpToDate

  https://www.uptodate.com/contents/clinical-manifestations-evaluation-and-diagnosis-of-acute-radiation-exposure

  The signs and symptoms of ARS are related to the type of radiation and the absorbed dose of radiation. […] Ionizing radiation can damage macromolecules (eg, DNA, RNA, proteins) and cellular components (eg, plasma membrane). Radiation effects can be direct (eg, single- or double-strand DNA breaks) or indirect (by interacting with water or other molecules to produce free radicals). […] Ionizing radiation has predictable dose- and time-dependent effects on hematopoiesis that are manifest as cytopenias (ie, neutropenia, lymphopenia, anemia, and thrombocytopenia) with resultant clinical consequences, including infections, weakness, and bleeding. […] Ionizing radiation can damage macromolecules (eg, DNA, RNA, proteins) and cellular components (eg, plasma membrane). Radiation effects can be direct (eg, single- or double-strand DNA breaks) or indirect (by interacting with water or other molecules to produce free radicals).

• #7 Acute radiation syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Acute_radiation_syndrome

  Acute radiation syndrome (ARS), also known as radiation sickness or radiation poisoning, is a collection of health effects that are caused by being exposed to high amounts of ionizing radiation in a short period of time. […] ARS involves a total dose of greater than 0.7 Gy (70 rad), that generally occurs from a source outside the body, delivered within a few minutes. […] At high doses, this causes DNA damage that may be irreparable. […] Exposure to high doses of radiation causes DNA damage, later creating serious and even lethal chromosomal aberrations if left unrepaired. […] Ionizing radiation can produce reactive oxygen species, and does directly damage cells by causing localized ionization events. […] Clustered damage takes longer to repair than isolated breakages, and is less likely to be repaired at all. […] Larger radiation doses are more prone to cause tighter clustering of damage, and closely localized damage is increasingly less likely to be repaired.

• #8 CBRNE – Radiation Emergencies: Overview, Terminology, Biologic Effects of Ionizing Radiation

  https://emedicine.medscape.com/article/834015-reference

  The principal pathologic effect of ionizing radiation results from damage to DNA. Regardless of the form of ionizing radiation, the common pathway of injury is that the radiation deposits a relatively large amount of energy into the electron orbitals of atoms in the biologic medium. This energy transfer raises the energy level (excites) of the electron and, if sufficient, ejects the electron from the atom, resulting in a now positively charged atom (ionization). […] These charged particles are chemically active, resulting in breakage of the chemical bonds within the DNA molecule. In addition to this direct injury, ionization radiation interacts with cellular water, forming free radicals, which can also damage the chemical bonds in the DNA strands. Regardless of the form of ionizing radiation (alpha, beta, gamma, x-ray, neutrons) or whether the damage is direct or indirect via free radical formation, the final pathologic injury is disruption of chemical bonds in the DNA strands. DNA damage is dose dependant, with the most common damage being single-strand breaks. As long as the number of breaks is not overwhelming and the complementary DNA template remains intact, these injuries are repaired with little biological consequence. In contrast, if the injury results in a double-strand break, the repair template is lost and can result in cell death, mutations, or carcinogenesis.

• #9 Clinical manifestations, evaluation, and diagnosis of acute radiation exposure – UpToDate

  https://www.uptodate.com/contents/clinical-manifestations-evaluation-and-diagnosis-of-acute-radiation-exposure

  The signs and symptoms of ARS are related to the type of radiation and the absorbed dose of radiation. […] Ionizing radiation can damage macromolecules (eg, DNA, RNA, proteins) and cellular components (eg, plasma membrane). Radiation effects can be direct (eg, single- or double-strand DNA breaks) or indirect (by interacting with water or other molecules to produce free radicals). […] Ionizing radiation has predictable dose- and time-dependent effects on hematopoiesis that are manifest as cytopenias (ie, neutropenia, lymphopenia, anemia, and thrombocytopenia) with resultant clinical consequences, including infections, weakness, and bleeding. […] Ionizing radiation can damage macromolecules (eg, DNA, RNA, proteins) and cellular components (eg, plasma membrane). Radiation effects can be direct (eg, single- or double-strand DNA breaks) or indirect (by interacting with water or other molecules to produce free radicals).

• #10 Clinical manifestations, evaluation, and diagnosis of acute radiation exposure – UpToDate

  https://www.uptodate.com/contents/clinical-manifestations-evaluation-and-diagnosis-of-acute-radiation-exposure

  Ionizing radiation has dose-dependent („deterministic”) effects with predictable thresholds for tissue reaction and severity of injury (eg, bone marrow suppression). Radiation also has a random („stochastic”) effect, whereby the dose affects the probability of an effect rather than severity of injury. […] Ionizing radiation can damage macromolecules (eg, DNA, RNA, proteins) and cellular components (eg, plasma membrane). Radiation effects can be direct (eg, single- or double-strand DNA breaks) or indirect (by interacting with water or other molecules to produce free radicals).

• #11 Radiation Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441931/

  Prolonged or significant exposure to ionizing radiation can result in acute radiation syndrome. The National Council on Radiation Protection and Measurements defines this as „a broad term used to describe a range of signs and symptoms that reflect severe damage to specific organ systems and that can lead to death within hours or up to several months after exposure.” […] Acute radiation syndrome can result from direct exposure or contamination by radioactive materials. Direct exposure can be caused by a nuclear blast, while contamination can result from the ingestion of nuclear-contaminated food, water, and skin contact with the nuclear material. Acute radiation syndrome is divided into 3 groups: hematopoietic, gastrointestinal, and cardiac/neurological systems. Each system will require a different dose of radiation to manifest the symptoms of acute radiation syndrome. The timing of symptoms is also subdivided into prodrome, latent, and manifest phases. […] Radiation is detrimental to body tissues based on how quickly their cells turn over. Those with a high mitotic index will be more severely affected at a lower dose. These include bone marrow, the gastrointestinal tract, and skin.

• #12 CBRNE – Radiation Emergencies: Overview, Terminology, Biologic Effects of Ionizing Radiation

  https://emedicine.medscape.com/article/834015-reference

  Since DNA damage is the principal cause of the biologic effects of radiation, tissues with a high turnover rate are more sensitive to the toxic effects of radiation than cells that are more differentiated. Cells and tissues can repair a certain amount of this damage with no apparent clinical consequence; however, at higher doses, normal homeostatic mechanisms are overwhelmed. Physiologically, damage on the chemical level progresses to cellular dysfunction, which leads to tissue dysfunction, then organ failure and, ultimately, to death. […] Early effects of radiation are seen after large doses of radiation are delivered over short periods and especially affect rapidly dividing, self-renewing organs including skin, bone marrow, and gut epithelium. Clinical syndromes reflect the failure of replenishment of tissues with rapid turn over and include acute radiation sickness and radiation burns. They are typically seen within a short period following a massive exposure.

• #13 Radiation sickness – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/radiation-sickness/symptoms-causes/syc-20377058

  Radiation sickness is damage to the body caused by a large dose of radiation often received over a short time. This is called acute radiation sickness. […] Radiation sickness is caused by being exposed to a high dose of radiation. Radiation is the energy released from atoms as either a wave or a tiny particle of matter. […] Radiation sickness happens when high-energy radiation damages or destroys certain cells in the body. Areas of the body most at risk of being affected by high-energy radiation are the bone marrow cells and the lining of the intestinal tract.

• #14 Radiation Injury – Injuries and Poisoning – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/injuries-and-poisoning/radiation-injury/radiation-injury

  Radiation injury is damage to tissues caused by exposure to ionizing radiation. […] Large doses of ionizing radiation can cause acute illness by reducing the production of blood cells and damaging the digestive tract. […] Radiation injury due to large and very large doses is referred to as a tissue reaction. The dose needed to cause visible tissue injury varies with tissue type. […] By changing molecules in the highly ordered environment of the cell, ionizing radiation can disrupt and damage cells. Depending on the magnitude of the dose, organs exposed, and types of radiation, cellular damage caused by ionizing radiation can cause acute illness, increase the risk of developing cancer, or both. […] The damaging effects of radiation (that is, the severity of the tissue reaction) depend on several factors: The amount (dose), how rapidly the dose is received, how much of the body is exposed, the sensitivity of particular tissues to radiation, the presence of genetic abnormalities that impair normal DNA repair, the person’s age at time of exposure, and the person’s general state of health prior to the exposure.

• #15 Radiobiology of the acute radiation syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3863296/

  Acute radiation syndrome or acute radiation sickness is classically subdivided into three subsyndromes: the hematopoietic, gastrointestinal and neurovascular syndrome but many other tissues can be damaged. […] Classical pathophysiology explain the failure of each of these organs and the timing of appearance of their signs and symptoms due to radiation-induced cytocidal effects of a great number of parenchymal cells of hierarchically organized tissues. […] Radiation-induced multi-organ involvement is thought to be due to radiation-induced systemic inflammatory response mediated by released pro-inflammatory cytokines. […] Classical radiobiology explain the failure of each of these organs by radiation-induced death (cytocidal effects) of a great number of parenchymal cells (target cell theory) but today we know that radiation not only cause lethal effects but also functional and indirect effects in many cells (multi-cellular target theory).

• #16 Radiobiology of the acute radiation syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3863296/

  Acute radiation syndrome or acute radiation sickness is classically subdivided into three subsyndromes: the hematopoietic, gastrointestinal and neurovascular syndrome but many other tissues can be damaged. […] Classical pathophysiology explain the failure of each of these organs and the timing of appearance of their signs and symptoms due to radiation-induced cytocidal effects of a great number of parenchymal cells of hierarchically organized tissues. […] Radiation-induced multi-organ involvement is thought to be due to radiation-induced systemic inflammatory response mediated by released pro-inflammatory cytokines. […] Classical radiobiology explain the failure of each of these organs by radiation-induced death (cytocidal effects) of a great number of parenchymal cells (target cell theory) but today we know that radiation not only cause lethal effects but also functional and indirect effects in many cells (multi-cellular target theory).

• #17 Radiobiology of the acute radiation syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3863296/

  The pathophysiological mechanism of radiation induced multiple organ failure is not clear but evidence has accumulated suggesting a major role of damaged endothelial cells leading to a radiation-induced systemic inflammatory response syndrome mediated by the release of inflammatory cytokines. […] The hypothesis is that the symptomatology of organ system involvement is not only due to the radiation-induced depletion of proliferating cells of rapid turnover tissues but also due to radiation-induced changes in the vascular system and specifically in the endothelial cells leading the development of an uncontrolled systemic inflammatory response. […] Moreover, the last two reported examples of large-field high-dose accidental irradiation in Tokai-mura and Nesvizh showed that after appropriate and extensive treatment, it is possible to bridge the acute phase of radiation-induced hematopoietic and gastrointestinal syndromes but sequentially new clinical findings involving other organs and cell system appear.

• #18 Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

  https://www.e-roj.org/journal/view.php?doi=10.3857/roj.2014.32.3.103

  Classically, normal tissue injury following high doses of radiation is thought to result from either depletion of parenchymal and/or vascular endothelial cells and attempts have been made to determine whether parenchymal or endothelial progenitors cells are the primary targets responsible for the tissue damage. […] More recent molecular and cellular studies suggest that dynamic secondary reactive processes in response to vascular endothelial cell and tissue stem and progenitor cell death leads to much greater cell loss, tissue damage, fibrosis, necrosis, and functional deficits. […] Excessive Generation of ROS Following Radiation […] Excessive Production of Cytokines and Chemokines […] Among the numerous pro-inflammatory cytokines and chemokines that are excessively produced immediately following radiation exposure, interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF)-, and transforming growth factor (TGF)- are major cytokines involved in the response of skin, lung, and brain.

• #19 Radiobiology of the acute radiation syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3863296/

  The pathophysiological mechanism of radiation induced multiple organ failure is not clear but evidence has accumulated suggesting a major role of damaged endothelial cells leading to a radiation-induced systemic inflammatory response syndrome mediated by the release of inflammatory cytokines. […] The hypothesis is that the symptomatology of organ system involvement is not only due to the radiation-induced depletion of proliferating cells of rapid turnover tissues but also due to radiation-induced changes in the vascular system and specifically in the endothelial cells leading the development of an uncontrolled systemic inflammatory response. […] Moreover, the last two reported examples of large-field high-dose accidental irradiation in Tokai-mura and Nesvizh showed that after appropriate and extensive treatment, it is possible to bridge the acute phase of radiation-induced hematopoietic and gastrointestinal syndromes but sequentially new clinical findings involving other organs and cell system appear.

• #20 Radiobiology of the acute radiation syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3863296/

  It has been shown that radiation response of central nervous system is characterized by local production of pro-inflammatory cytokines in different brain structures causing a stimulation of inflammatory cascade, interaction with other inflammatory mediators and upregulation of the inflammatory process that leads to neurotoxicity. […] These alterations in endothelial cell integrity and function could play a critical role in mediating organ dysfunction after acute radiation exposure.

• #21 In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury | Scientific Reports

  https://www.nature.com/articles/srep15738

  The pathophysiological mechanism involved in side effects of radiation therapy and especially the role of the endothelium remains unclear. […] This work shows that PAI-1 plays a role in radiation-induced intestinal injury by an endothelium-dependent mechanism and demonstrates in vivo that the endothelium is directly involved in the progression of radiation-induced enteritis. […] The contemporary view involves several cell types and molecular mechanisms, which together form an orchestrated response and contribute to the initiation, progression and chronicity of radiation-induced injury. […] Irradiation leads to endothelial cell apoptosis, increased vascular permeability and acquisition of a pro-inflammatory and pro-coagulant phenotype. […] We previously showed that PAI-1 total knockout mice are protected against radiation enteritis, but there was no evidence that this was dependent on the PAI-1 endothelial pool.

• #22 Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

  https://www.e-roj.org/journal/view.php?doi=10.3857/roj.2014.32.3.103

  To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. […] The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. […] Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. […] Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues.

• #23 Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

  https://www.e-roj.org/journal/view.php?doi=10.3857/roj.2014.32.3.103

  Classically, normal tissue injury following high doses of radiation is thought to result from either depletion of parenchymal and/or vascular endothelial cells and attempts have been made to determine whether parenchymal or endothelial progenitors cells are the primary targets responsible for the tissue damage. […] More recent molecular and cellular studies suggest that dynamic secondary reactive processes in response to vascular endothelial cell and tissue stem and progenitor cell death leads to much greater cell loss, tissue damage, fibrosis, necrosis, and functional deficits. […] Excessive Generation of ROS Following Radiation […] Excessive Production of Cytokines and Chemokines […] Among the numerous pro-inflammatory cytokines and chemokines that are excessively produced immediately following radiation exposure, interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF)-, and transforming growth factor (TGF)- are major cytokines involved in the response of skin, lung, and brain.

• #24 Mechanisms Involved in Chronic Radiation Exposure Effects: Pathogenesis of Chronic Radiation Syndrome | Radiology Key

  https://radiologykey.com/mechanisms-involved-in-chronic-radiation-exposure-effects-pathogenesis-of-chronic-radiation-syndrome/

  Each type of radiation produces certain ionization density and has its own penetrating power which is characterized by different linear energy transfer. […] The understanding of energy transfer along the tracks of IR, when they pass through the DNA molecules, has improved significantly in recent years. […] Ionization results in damaged chemical bonds in DNA molecules. […] Thus, high-LET radiation effect is capable of creating very large ionization clusters, which low-LET radiation does not form. […] The presence of the oxygen in the internal medium promotes increase in reactive oxygen species yield and thus enhances radiation effects. […] The oxidative modification of bases in the DNA of normal cells results from the effects of various ROS. […] It is established that oxygen plays an extremely important role in the radiation cell damage.

• #25 Radiation Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441931/

  Prolonged or significant exposure to ionizing radiation can result in acute radiation syndrome. The National Council on Radiation Protection and Measurements defines this as „a broad term used to describe a range of signs and symptoms that reflect severe damage to specific organ systems and that can lead to death within hours or up to several months after exposure.” […] Acute radiation syndrome can result from direct exposure or contamination by radioactive materials. Direct exposure can be caused by a nuclear blast, while contamination can result from the ingestion of nuclear-contaminated food, water, and skin contact with the nuclear material. Acute radiation syndrome is divided into 3 groups: hematopoietic, gastrointestinal, and cardiac/neurological systems. Each system will require a different dose of radiation to manifest the symptoms of acute radiation syndrome. The timing of symptoms is also subdivided into prodrome, latent, and manifest phases. […] Radiation is detrimental to body tissues based on how quickly their cells turn over. Those with a high mitotic index will be more severely affected at a lower dose. These include bone marrow, the gastrointestinal tract, and skin.

• #26 Acute Radiation Syndrome: Information for Clinicians | Radiation Emergencies | CDC

  https://www.cdc.gov/radiation-emergencies/hcp/clinical-guidance/ars.html

  Acute Radiation Syndrome (ARS) (sometimes known as acute radiation sickness) is an acute illness caused by radiation exposure (or irradiation) of the entire body (or most of the body) by a high dose of penetrating radiation in a very short period of time (usually a matter of minutes). […] The major cause of this syndrome is depletion of immature parenchymal stem cells in specific tissues. […] The required conditions for Acute Radiation Syndrome (ARS) are […] The radiation dose must be large (i.e., greater than 0.7 Gray (Gy) or 70 rads). […] The dose usually must be external (i.e., the source of radiation is outside of the patient’s body). […] The radiation must be penetrating (i.e., able to reach the internal organs). […] The entire body (or a significant portion of it) must have received the dose.

• #27 Radiation sickness | PPT

  https://www.slideshare.net/slideshow/radiation-sickness-176759491/176759491

  Alpha, beta, gamma, and neutron radiation can damage tissues depending on their penetrability. Acute radiation syndrome results from a high whole body radiation dose and involves the bone marrow, GI tract, and cardiovascular systems. Symptoms include nausea, vomiting, and hemorrhage. Management involves stabilization, decontamination, treatment of injuries, and monitoring blood counts to determine prognosis. Long term effects include increased cancer risk. […] Acute Radiation Syndrome (ARS) is an acute illness caused by irradiation of the entire body by a high dose of penetrating radiation in a very short period of time). The major cause of this syndrome is depletion of immature parenchymal stem cells in specific tissues. […] The required conditions for Acute Radiation Syndrome (ARS) are: The radiation dose must be large (i.e greater than 0.7 Gray (Gy). The dose usually must be external (i.e., the source of radiation is outside of the patients body). The radiation must be penetrating i.e., able to reach the internal organs The entire body (or a significant portion of it) must have received the dose. The dose must have been delivered in a short time.

• #28 Understanding Radiation Sickness: Symptoms, Causes, and Treatment of Acute Radiation Syndrome – Raybloc X-ray Protection

  https://raybloc.com/radiation-sickness/

  Bone Marrow Syndrome, also known as Hematopoietic Syndrome, typically occurs with radiation exposure ranging from 0.7 to 10 Gray (Gy). This syndrome primarily affects the body’s blood cell production. The bone marrow, a crucial site for producing blood cells, becomes damaged, leading to a decrease in red cells, white cells, and platelets. This decline can result in anemia, increased risk of infection, and impaired blood clotting, posing significant health risks. […] Gastrointestinal Syndrome is usually seen with higher doses of radiation, typically between 10 to 50 Gy. This level of exposure causes severe damage to the lining of the gastrointestinal tract, from the stomach to the intestines. Symptoms often include nausea, vomiting, loss of appetite, abdominal pain, and severe diarrhoea. […] Exposure to radiation levels above 50 Gy can lead to Cardiovascular/Central Nervous System Syndrome. This is the most severe form of radiation syndrome and is often fatal. At these high doses, radiation causes immediate damage to the heart and brain.

• #29 Radiation sickness | PPT

  https://www.slideshare.net/slideshow/radiation-sickness-176759491/176759491

  The three classic ARS Syndromes are Bone marrow syndrome: the full syndrome will usually occur with a dose greater than approximately 0.7 The survival rate of patients with this syndrome decreases with increasing dose. The primary cause of death is the destruction of the bone marrow, resulting in infection and hemorrhage. Gastrointestinal (GI) syndrome: the full syndrome will usually occur with a dose greater than approximately 10 Gy (1000 rads) Survival is extremely unlikely with this syndrome Destructive and irreparable changes in the GI tract and bone marrow usually cause infection, dehydration, and electrolyte imbalance. Death usually occurs within 2 weeks. Cardiovascular (CV)/ Central Nervous System (CNS) syndrome: the full syndrome will usually occur with a dose greater than approximately 50 Gy Death occurs within 3 days. Death likely is due to collapse of the circulatory system as well as increased pressure in the confining cranial vault as the result of increased fluid content caused by edema, vasculitis, and meningitis.

• #30 Acute Radiation Syndrome : How Does Radiation Sickness Work? – CheckOrphan

  https://checkorphan.org/video/acute-radiation-syndrome-how-does-radiation-sickness-work/

  Acute Radiation Syndrome (ARS) (sometimes known as radiation toxicity or radiation sickness) is an acute illness caused by irradiation of the entire body (or most of the body) by a high dose of penetrating radiation in a very short period of time (usually a matter of minutes). […] The primary cause of death is the destruction of the bone marrow, resulting in infection and hemorrhage. […] Damage to the gastrointestinal tract is one of the primary causes of morbidity and mortality following radiation exposure. […] Death likely is due to collapse of the circulatory system as well as increased pressure in the confining cranial vault as the result of increased fluid content caused by edema, vasculitis, and meningitis.

• #31 Acute Radiation Syndrome: Information for Clinicians | Radiation Emergencies | CDC

  https://www.cdc.gov/radiation-emergencies/hcp/clinical-guidance/ars.html

  The dose must have been delivered in a short time (usually a matter of minutes). […] The primary cause of death is the destruction of the bone marrow, resulting in infection and hemorrhage. […] Destructive and irreparable changes in the GI tract and bone marrow usually cause infection, dehydration, and electrolyte imbalance. […] Death likely is due to collapse of the circulatory system as well as increased pressure in the confining cranial vault as the result of increased fluid content caused by edema, vasculitis, and meningitis. […] The classic symptoms for this stage are nausea, vomiting, as well as anorexia and possibly diarrhea (depending on dose), which occur from minutes to days following exposure. […] When the basal cell layer of the skin is damaged by radiation, inflammation, erythema, and dry or moist desquamation can occur. […] In most cases, healing occurs by regenerative means. However, very large skin doses can cause permanent hair loss, damaged sebaceous and sweat glands, atrophy, fibrosis, decreased or increased skin pigmentation, and ulceration or necrosis of the exposed tissue.

• #32 Radiation sickness | PPT

  https://www.slideshare.net/slideshow/radiation-sickness-176759491/176759491

  The three classic ARS Syndromes are Bone marrow syndrome: the full syndrome will usually occur with a dose greater than approximately 0.7 The survival rate of patients with this syndrome decreases with increasing dose. The primary cause of death is the destruction of the bone marrow, resulting in infection and hemorrhage. Gastrointestinal (GI) syndrome: the full syndrome will usually occur with a dose greater than approximately 10 Gy (1000 rads) Survival is extremely unlikely with this syndrome Destructive and irreparable changes in the GI tract and bone marrow usually cause infection, dehydration, and electrolyte imbalance. Death usually occurs within 2 weeks. Cardiovascular (CV)/ Central Nervous System (CNS) syndrome: the full syndrome will usually occur with a dose greater than approximately 50 Gy Death occurs within 3 days. Death likely is due to collapse of the circulatory system as well as increased pressure in the confining cranial vault as the result of increased fluid content caused by edema, vasculitis, and meningitis.

• #33 Understanding Radiation Sickness: Symptoms, Causes, and Treatment of Acute Radiation Syndrome – Raybloc X-ray Protection

  https://raybloc.com/radiation-sickness/

  Bone Marrow Syndrome, also known as Hematopoietic Syndrome, typically occurs with radiation exposure ranging from 0.7 to 10 Gray (Gy). This syndrome primarily affects the body’s blood cell production. The bone marrow, a crucial site for producing blood cells, becomes damaged, leading to a decrease in red cells, white cells, and platelets. This decline can result in anemia, increased risk of infection, and impaired blood clotting, posing significant health risks. […] Gastrointestinal Syndrome is usually seen with higher doses of radiation, typically between 10 to 50 Gy. This level of exposure causes severe damage to the lining of the gastrointestinal tract, from the stomach to the intestines. Symptoms often include nausea, vomiting, loss of appetite, abdominal pain, and severe diarrhoea. […] Exposure to radiation levels above 50 Gy can lead to Cardiovascular/Central Nervous System Syndrome. This is the most severe form of radiation syndrome and is often fatal. At these high doses, radiation causes immediate damage to the heart and brain.

• #34 Acute Radiation Syndrome: Information for Clinicians | Radiation Emergencies | CDC

  https://www.cdc.gov/radiation-emergencies/hcp/clinical-guidance/ars.html

  The dose must have been delivered in a short time (usually a matter of minutes). […] The primary cause of death is the destruction of the bone marrow, resulting in infection and hemorrhage. […] Destructive and irreparable changes in the GI tract and bone marrow usually cause infection, dehydration, and electrolyte imbalance. […] Death likely is due to collapse of the circulatory system as well as increased pressure in the confining cranial vault as the result of increased fluid content caused by edema, vasculitis, and meningitis. […] The classic symptoms for this stage are nausea, vomiting, as well as anorexia and possibly diarrhea (depending on dose), which occur from minutes to days following exposure. […] When the basal cell layer of the skin is damaged by radiation, inflammation, erythema, and dry or moist desquamation can occur. […] In most cases, healing occurs by regenerative means. However, very large skin doses can cause permanent hair loss, damaged sebaceous and sweat glands, atrophy, fibrosis, decreased or increased skin pigmentation, and ulceration or necrosis of the exposed tissue.

• #35 Radiation Proctitis and Management Strategies

  https://www.e-ce.org/journal/view.php?doi=10.5946/ce.2020.288

  PATHOGENESIS OF RADIATION PROCTITIS The pathogenesis of RP is complex and yet to be fully understood. To better comprehend the pathogenic process, it is divided into two sections. Mechanism of radiation-mediated tissue damage It is essential to first understand the mechanism by which ionizing radiation causes damage to tissues at the cellular level. The damage to tissues secondary to RT is widespread; however, in essence, both direct and indirect mechanisms of tissue damage via radiation target cellular deoxyribonucleic acid (DNA), thereby inhibiting transcription and preventing cellular replication. Through the direct mechanism, ionizing radiation directly damages the DNA or cell membrane. It can induce double-stranded DNA breaks, cause inter- and intra-strand cross-linkages, or mutations of the DNA and can compromise the rigidity of the phospholipid bilayer and the electrical gradient of the cell membrane. The indirect mechanism involves the generation of free radicals from the ionization of water molecules, leading to oxidative stress injuries. However, as this radiation-induced damage is in process, DNA repair mechanisms are activated to fix the DNA strands. At low doses of radiation, the repair mechanisms are successful and lead to the resolution of DNA injuries. However, at higher doses, the ionizing radiation can overwhelm the DNA repair mechanism, leading to apoptosis of the cell or inhibition of mitosis. It is also important to note that cells with high rates of mitosis, such as stem cells and cancers, are most affected by RT. Tissue response to radiation and pathogenesis of radiation proctitis The mucosa of the GI tract is highly proliferative. As per the literature, enterocytes have the highest turnover rate of any fixed cell in the body. Hence, the rapidly dividing mucosal stem cells present within the crypts of Lieberkhn are highly susceptible to radiation injury. Initiation of RP occurs via radiation-induced damage to the mucosa, followed by late indolent connective tissue growth and remodeling, and subsequently tissue response to the ongoing ischemia. Damage to the rapidly dividing intestinal crypt stem cells in the radiation field leads to their depletion, resulting in crypt involution, mucosal injury, and exposure of the underlying lamina propria to luminal bacteria. An acute inflammatory response may be generated after exposure to the bacteria, often involving T-lymphocytes, macrophages, and neutrophils. Additional damage to the extracellular matrix, mucosa, and submucosa of the bowel wall may be secondary to the production of enzymes and reactive oxygen species. On gross visualization, early radiation injury will show edema, mucosal hyperemia, and ulceration of the tissue. Histological changes of early radiation damage may be seen within a few hours of RT, followed by infiltration of leukocytes and crypt abscess formation in 24 weeks. Subsequently, progressive occlusive vasculitis with foam cell invasion of the intima and hyaline thickening of the media of arterioles may be seen, which contributes to obliterative endarteritis, leading to full-thickness ischemia of the bowel wall. After cessation of RT, the acute inflammatory process subsides, and intestinal crypt cells start to regenerate. Animal models suggest that migration and engraftment of stem cells from the bone marrow may be responsible for the repair of damaged crypts. However, in some patients, for reasons unknown, the inflammatory process may exaggerate, leading to ulceration of the mucosa followed by fibrosis and the development of chronic inflammatory changes. Additionally, radiation can directly damage the vascular and endothelial cells leading to full-thickness bowel ischemia; hence, it plays a major role in the pathogenesis of RP.

• #36 Research progress and treatment of radiation enteritis and gut microbiota

  https://www.e-roj.org/journal/view.php?doi=10.3857/roj.2023.00346

  Treatment methods such as probiotics, antibiotics, and fecal microbiota transplantation are ways to correct the microbiota and may be an effective way to prevent and treat radiation enteritis. […] Radiation enteritis, which refers to radiation therapy-induced injury to the intestinal epithelium, with or without mild inflammation, is one of the common complications after radiation therapy in patients with pelvic malignancy. […] The basic pathological changes include two aspects: intestinal mucosal injury caused by radiation and vascular connective tissue injury caused by radiation vascular endothelial cells. […] At the initial stage of injury, the proliferation and maturation of intestinal epithelial cells with the ability of rapid division appear abnormal, which leads to reduced mitosis of crypt cells and then leads to thinning of the intestinal mucosa and shortening of the intestinal villi.

• #37 Research progress and treatment of radiation enteritis and gut microbiota

  https://www.e-roj.org/journal/view.php?doi=10.3857/roj.2023.00346

  Radiation enteritis is a kind of intestinal radiation injury in patients with pelvic and retroperitoneal malignancies after radiotherapy, and its occurrence and development process are very complicated. […] At present, studies have confirmed that intestinal microecological imbalance is an important factor in the formation of this disease. […] Abdominal radiation causes changes in the composition of the flora and a decrease in its diversity, which is mainly manifested by a decrease in beneficial bacterial species such as Lactobacilli and Bifidobacteria. […] Intestinal dysbacteriosis aggravates radiation enteritis, weakens the function of the intestinal epithelial barrier, and promotes the expression of inflammatory factors, thereby aggravating the occurrence of enteritis. […] Given the role of the microbiome in radiation enteritis, we suggest that the gut microbiota may be a potential biomarker for the disease.

• #38 Research progress and treatment of radiation enteritis and gut microbiota

  https://www.e-roj.org/journal/view.php?doi=10.3857/roj.2023.00346

  This results in intestinal necrosis, intestinal fistula, intestinal perforation, and intestinal obstruction. […] Existing research results show that the gut microbiota of patients with radiation enteritis is significantly translocated, the number of Actinobacteriota and Proteobacteria is significantly increased, and many conditional pathogenic bacteria, such as Enterococcus and Enterobacterales, are included. […] In summary, the study mentioned above shows that the gut microbiota of the patients with radiation enteritis changes significantly in terms of composition and diversity. […] The number of beneficial bacteria (such as Lactobacillus) from Firmicutes and Bacteroidetes decreased significantly. […] The decrease in the number of beneficial bacteria will promote the proliferation of opportunistic pathogens and promote the release of endotoxins, thus aggravating the intestinal inflammatory response, inducing damage to the intestinal mucosal barrier, and aggravating the disease of patients.

• #39 Radiation Proctitis and Management Strategies

  https://www.e-ce.org/journal/view.php?doi=10.5946/ce.2020.288

  PATHOGENESIS OF RADIATION PROCTITIS The pathogenesis of RP is complex and yet to be fully understood. To better comprehend the pathogenic process, it is divided into two sections. Mechanism of radiation-mediated tissue damage It is essential to first understand the mechanism by which ionizing radiation causes damage to tissues at the cellular level. The damage to tissues secondary to RT is widespread; however, in essence, both direct and indirect mechanisms of tissue damage via radiation target cellular deoxyribonucleic acid (DNA), thereby inhibiting transcription and preventing cellular replication. Through the direct mechanism, ionizing radiation directly damages the DNA or cell membrane. It can induce double-stranded DNA breaks, cause inter- and intra-strand cross-linkages, or mutations of the DNA and can compromise the rigidity of the phospholipid bilayer and the electrical gradient of the cell membrane. The indirect mechanism involves the generation of free radicals from the ionization of water molecules, leading to oxidative stress injuries. However, as this radiation-induced damage is in process, DNA repair mechanisms are activated to fix the DNA strands. At low doses of radiation, the repair mechanisms are successful and lead to the resolution of DNA injuries. However, at higher doses, the ionizing radiation can overwhelm the DNA repair mechanism, leading to apoptosis of the cell or inhibition of mitosis. It is also important to note that cells with high rates of mitosis, such as stem cells and cancers, are most affected by RT. Tissue response to radiation and pathogenesis of radiation proctitis The mucosa of the GI tract is highly proliferative. As per the literature, enterocytes have the highest turnover rate of any fixed cell in the body. Hence, the rapidly dividing mucosal stem cells present within the crypts of Lieberkhn are highly susceptible to radiation injury. Initiation of RP occurs via radiation-induced damage to the mucosa, followed by late indolent connective tissue growth and remodeling, and subsequently tissue response to the ongoing ischemia. Damage to the rapidly dividing intestinal crypt stem cells in the radiation field leads to their depletion, resulting in crypt involution, mucosal injury, and exposure of the underlying lamina propria to luminal bacteria. An acute inflammatory response may be generated after exposure to the bacteria, often involving T-lymphocytes, macrophages, and neutrophils. Additional damage to the extracellular matrix, mucosa, and submucosa of the bowel wall may be secondary to the production of enzymes and reactive oxygen species. On gross visualization, early radiation injury will show edema, mucosal hyperemia, and ulceration of the tissue. Histological changes of early radiation damage may be seen within a few hours of RT, followed by infiltration of leukocytes and crypt abscess formation in 24 weeks. Subsequently, progressive occlusive vasculitis with foam cell invasion of the intima and hyaline thickening of the media of arterioles may be seen, which contributes to obliterative endarteritis, leading to full-thickness ischemia of the bowel wall. After cessation of RT, the acute inflammatory process subsides, and intestinal crypt cells start to regenerate. Animal models suggest that migration and engraftment of stem cells from the bone marrow may be responsible for the repair of damaged crypts. However, in some patients, for reasons unknown, the inflammatory process may exaggerate, leading to ulceration of the mucosa followed by fibrosis and the development of chronic inflammatory changes. Additionally, radiation can directly damage the vascular and endothelial cells leading to full-thickness bowel ischemia; hence, it plays a major role in the pathogenesis of RP.

• #40 Radiation sickness | PPT

  https://www.slideshare.net/slideshow/radiation-sickness-176759491/176759491

  The three classic ARS Syndromes are Bone marrow syndrome: the full syndrome will usually occur with a dose greater than approximately 0.7 The survival rate of patients with this syndrome decreases with increasing dose. The primary cause of death is the destruction of the bone marrow, resulting in infection and hemorrhage. Gastrointestinal (GI) syndrome: the full syndrome will usually occur with a dose greater than approximately 10 Gy (1000 rads) Survival is extremely unlikely with this syndrome Destructive and irreparable changes in the GI tract and bone marrow usually cause infection, dehydration, and electrolyte imbalance. Death usually occurs within 2 weeks. Cardiovascular (CV)/ Central Nervous System (CNS) syndrome: the full syndrome will usually occur with a dose greater than approximately 50 Gy Death occurs within 3 days. Death likely is due to collapse of the circulatory system as well as increased pressure in the confining cranial vault as the result of increased fluid content caused by edema, vasculitis, and meningitis.

• #41 Understanding Radiation Sickness: Symptoms, Causes, and Treatment of Acute Radiation Syndrome – Raybloc X-ray Protection

  https://raybloc.com/radiation-sickness/

  Bone Marrow Syndrome, also known as Hematopoietic Syndrome, typically occurs with radiation exposure ranging from 0.7 to 10 Gray (Gy). This syndrome primarily affects the body’s blood cell production. The bone marrow, a crucial site for producing blood cells, becomes damaged, leading to a decrease in red cells, white cells, and platelets. This decline can result in anemia, increased risk of infection, and impaired blood clotting, posing significant health risks. […] Gastrointestinal Syndrome is usually seen with higher doses of radiation, typically between 10 to 50 Gy. This level of exposure causes severe damage to the lining of the gastrointestinal tract, from the stomach to the intestines. Symptoms often include nausea, vomiting, loss of appetite, abdominal pain, and severe diarrhoea. […] Exposure to radiation levels above 50 Gy can lead to Cardiovascular/Central Nervous System Syndrome. This is the most severe form of radiation syndrome and is often fatal. At these high doses, radiation causes immediate damage to the heart and brain.

• #42 Acute Radiation Syndrome: Information for Clinicians | Radiation Emergencies | CDC

  https://www.cdc.gov/radiation-emergencies/hcp/clinical-guidance/ars.html

  The dose must have been delivered in a short time (usually a matter of minutes). […] The primary cause of death is the destruction of the bone marrow, resulting in infection and hemorrhage. […] Destructive and irreparable changes in the GI tract and bone marrow usually cause infection, dehydration, and electrolyte imbalance. […] Death likely is due to collapse of the circulatory system as well as increased pressure in the confining cranial vault as the result of increased fluid content caused by edema, vasculitis, and meningitis. […] The classic symptoms for this stage are nausea, vomiting, as well as anorexia and possibly diarrhea (depending on dose), which occur from minutes to days following exposure. […] When the basal cell layer of the skin is damaged by radiation, inflammation, erythema, and dry or moist desquamation can occur. […] In most cases, healing occurs by regenerative means. However, very large skin doses can cause permanent hair loss, damaged sebaceous and sweat glands, atrophy, fibrosis, decreased or increased skin pigmentation, and ulceration or necrosis of the exposed tissue.

• #43 Cerebrovascular Acute Radiation Syndrome : Radiation Neurotoxins, Mechanisms of Toxicity, Neuroimmune Interactions. – ADS

  http://ui.adsabs.harvard.edu/abs/2010cosp…38.3535P/abstract

  Cerebrovascular Acute Radiation Syndrome (CvARS) is an extremely severe injury of Central Nervous System (CNS) and Peripheral Nervous System (PNS). CvARS can be induced by the high doses of neutron, heavy ions, or gamma radiation. […] The radiation toxins, Cerebro-Vascular Radiation Neurotoxins (SvARSn), determine development of the acute radiation syndrome. Mechanism of action of the toxins: Though pathogenesis of radiation injury of CNS remains unknown, our concept describes the Cv ARS as a result of Neurotoxicity and Excitotoxicity, cell death through apoptotic necrosis. Neurotoxicity occurs after the high doses radiation exposure, formation of radiation neuro-toxins, possible bioradicals, or group of specific enzymes. […] Disruption of blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCFB) is possibly the most significant effect of microcirculation disorder and metabolic insufficiency. NMDA-receptors excitotoxic injury mediated by cerebral ischemia and cerebral hypoxia.

• #44 Radiobiology of the acute radiation syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3863296/

  It has been shown that radiation response of central nervous system is characterized by local production of pro-inflammatory cytokines in different brain structures causing a stimulation of inflammatory cascade, interaction with other inflammatory mediators and upregulation of the inflammatory process that leads to neurotoxicity. […] These alterations in endothelial cell integrity and function could play a critical role in mediating organ dysfunction after acute radiation exposure.

• #45 Cerebrovascular Acute Radiation Syndrome : Radiation Neurotoxins, Mechanisms of Toxicity, Neuroimmune Interactions. – ADS

  http://ui.adsabs.harvard.edu/abs/2010cosp…38.3535P/abstract

  Neurotoxicity and Excitotoxicity are two stages of the pathological processes resulted in damaging and killing nerve cells through apoptotic necrosis. Excitotoxicity is well known as a pathological process that occurs when important excitatory neurotransmitters (glutamate, serotonin) over-activate the receptors – NMDA, AMPA, 5HT1, 5HT2, 5H3. Radiation Neurotoxins possibly act on the same receptors and activate the cell death mechanisms through direct or indirect excessive activation of same receptors.

• #46 Molecular Pathogenesis of Radiation-Induced Cell Toxicity in Stem Cells

  https://www.mdpi.com/1422-0067/18/12/2749

  The DDR pathway is mediated by ATM and ATR as well as by two checkpoint effector kinases, Chk1 and Chk2, which are selectively phosphorylated and activated by ATM and ATR, respectively, to trigger a wide range of distinct downstream responses. […] In response to ionizing radiation, ATM is recruited to the site of DNA damage and acts as a sensor that initiates ATM activation in conjunction with the MRE11-RAD50-NBS1 proteins (MRN complex). […] The sensitivity of SCs to a genotoxic stress varies greatly depending on their type and developmental stage. […] The features that CSCs share with SC are not only self-renewal and differentiation but also high tumorigenic potential, and CSCs are also called tumor-initiating cells. […] Radiation induces the CSC phenotype in many cancers, including breast, lung, liver and prostate cancers, as well as melanoma.

• #47 Molecular Pathogenesis of Radiation-Induced Cell Toxicity in Stem Cells

  https://www.mdpi.com/1422-0067/18/12/2749

  The DDR pathway is mediated by ATM and ATR as well as by two checkpoint effector kinases, Chk1 and Chk2, which are selectively phosphorylated and activated by ATM and ATR, respectively, to trigger a wide range of distinct downstream responses. […] In response to ionizing radiation, ATM is recruited to the site of DNA damage and acts as a sensor that initiates ATM activation in conjunction with the MRE11-RAD50-NBS1 proteins (MRN complex). […] The sensitivity of SCs to a genotoxic stress varies greatly depending on their type and developmental stage. […] The features that CSCs share with SC are not only self-renewal and differentiation but also high tumorigenic potential, and CSCs are also called tumor-initiating cells. […] Radiation induces the CSC phenotype in many cancers, including breast, lung, liver and prostate cancers, as well as melanoma.

• #48 Mechanisms Involved in Chronic Radiation Exposure Effects: Pathogenesis of Chronic Radiation Syndrome | Radiology Key

  https://radiologykey.com/mechanisms-involved-in-chronic-radiation-exposure-effects-pathogenesis-of-chronic-radiation-syndrome/

  The development of oxidative process in the form of oxidation chain reactions in biomembranes is a mechanism of primary lesions enhancement, which ends in irreversible oxidative degradation of cell membrane structures. […] The mechanisms of oxidative degradation of biomembranes have been thoroughly studied. […] The study of cell and tissue reactions to low dose rate has fundamental importance for understanding the mechanisms of adaptation to chronic radiation effects. […] It is well known that the most dangerous consequences of cell exposure are caused by radiation damage to their nuclei. […] Initial DNA damage triggers various defense mechanisms aimed at compensatory mechanisms mobilization and activation of damaged structures reparation. […] The assumption that DNA reaction activity to damage and its repair process are the main determinants of the dose, dose rate, and radiation quality effects at the cell level was confirmed in different studies of the cells.

• #49 Mechanisms Involved in Chronic Radiation Exposure Effects: Pathogenesis of Chronic Radiation Syndrome | Radiology Key

  https://radiologykey.com/mechanisms-involved-in-chronic-radiation-exposure-effects-pathogenesis-of-chronic-radiation-syndrome/

  The first consequence of transcription activation, induced by p53, is the cell cycle block in checkpoints to prevent the multiplication of the appeared DNA defects by means of DNA reparation. […] Thus, the cells exposed to -radiation are blocked at the stages G1 and G2. […] DNA reparation begins almost immediately after the damage occurrence. […] The process of DNA structure damage recovery with reparation enzymes is preceded by chromatin transformations or translocation of chromosomes loci in the cell nucleus. […] The intensity of mutagenesis depends on the genotype of an organism, which determines the activity of repair and antioxidant systems. […] The development of tissue reactions may be due to the activity of cytokines and other mediators from damaged cells, leading to both the disturbance of cell function and cell death.

• #50 Molecular Pathogenesis of Radiation-Induced Cell Toxicity in Stem Cells

  https://www.mdpi.com/1422-0067/18/12/2749

  Radiation therapy is an effective cancer therapy, but damage to normal tissues surrounding the tumor due to radiotherapy causes severe complications. […] The pathogenesis of normal tissue response to radiation is complex and involves different mechanisms such as DNA damage repair, cell death, inflammation, angiogenesis and matrix remodeling, depending on the radiation dose and time course. […] To understand the mechanism of radiation-induced toxicity, observation of molecular changes in SCs and CSCs due to radiation treatment will have an important influence on the development of clinical therapy. […] The biological effects of radiation treatment depend on the total dose, fractionation rate, radiosensitivity and linear energy transfer (LET) in tumors. […] The indirect effects also include phenomena such as the “bystander effect”.

• #51 Acute Vs Chronic, Tissue Sensitivities To Radiation And [4 Cell Damage Pathways] For Radiologic Technologists • How Radiology Works

  https://howradiologyworks.com/acute-vs-chronic/

  Cell Death (First Generation): The damage is too severe to repair and the cell dies directly. One mechanism that can be responsible for this is apoptosis (programmed cell death), which helps organisms survive by not propagating mutations. Cell death is the primary cause of acute radiation sicknesses at very high levels of radiation dose. […] Cell Death (Second Generation): In some cases the damage is not significant enough to cause cell death directly but when the cell attempts to divide there is too much damage for the second generation (i.e. daughter cells) to survive. […] Mutation Propagated: When the cell damage is not repaired directly and the cell does not die it is possible that the mutation is passed on, or propagated. This is the mechanism for cancer induction (i.e. carcinogenesis). […] Acute radiation syndrome is caused by cell death. […] Cancer induction (carcinogenesis) is caused by mutations being propagated.

• #52 Radiation sickness – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/radiation-sickness/symptoms-causes/syc-20377058

  Radiation sickness is damage to the body caused by a large dose of radiation often received over a short time. This is called acute radiation sickness. […] Radiation sickness is caused by being exposed to a high dose of radiation. Radiation is the energy released from atoms as either a wave or a tiny particle of matter. […] Radiation sickness happens when high-energy radiation damages or destroys certain cells in the body. Areas of the body most at risk of being affected by high-energy radiation are the bone marrow cells and the lining of the intestinal tract.

• #53 Radiation-induced heart disease: a review of classification, mechanism and prevention

  https://www.ijbs.com/v15p2128.htm

  ROS can not only directly damage the intracellular macromolecular structure, but also altered the expression of multiple proteomes in the cytoplasm, activation of pro-inflammatory factors in connection with ROS. […] Cell apoptosis and necrosis occur in various types of cells in the heart after exposure to radiation, among which mitochondrial dysfunction and irreversible damage are the key links of cell apoptosis and necrosis, and the occurrence of mitochondrial dysfunction is closely related to endoplasmic reticulum(ER)stress. […] With the development of research, several studies have indicated that micro-RNAs (miRNAs) play an important role in the occurrence and progression of RIHD.

• #54 Radiation-induced kidney toxicity: molecular and cellular pathogenesis | Radiation Oncology | Full Text

  https://ro-journal.biomedcentral.com/articles/10.1186/s13014-021-01764-y

  In RN, the initial renal cell injury, which may start the cascade towards CKD, are DSB of the DNA through ionizing radiation, either by direct ionization events in the DNA or indirectly via mediation of water ionization products and/or reactive oxygen species. […] Cytokines released upon cell death, cellular senescence, and ionizing radiation itself trigger chronic inflammation. Finally, chronic inflammation and cellular senescence may lead to renal fibrosis. […] The reninangiotensinaldosterone system (RAAS) consists of enzymes and their peptide substrates and involves multiple organs. […] RAAS-inhibition with captopril mitigated RN in a randomized controlled trial in patients after 14 Gy TBI in 9 fractions with kidney shielding yielding a total dose of 9.8 Gy in preparation for BMT.

• #55 Molecular Pathogenesis of Radiation-Induced Cell Toxicity in Stem Cells

  https://www.mdpi.com/1422-0067/18/12/2749

  Radiation therapy is an effective cancer therapy, but damage to normal tissues surrounding the tumor due to radiotherapy causes severe complications. […] The pathogenesis of normal tissue response to radiation is complex and involves different mechanisms such as DNA damage repair, cell death, inflammation, angiogenesis and matrix remodeling, depending on the radiation dose and time course. […] To understand the mechanism of radiation-induced toxicity, observation of molecular changes in SCs and CSCs due to radiation treatment will have an important influence on the development of clinical therapy. […] The biological effects of radiation treatment depend on the total dose, fractionation rate, radiosensitivity and linear energy transfer (LET) in tumors. […] The indirect effects also include phenomena such as the “bystander effect”.

• #56 Radiation sickness | PPT

  https://www.slideshare.net/slideshow/radiation-sickness-176759491/176759491

  The four stages of ARS are: Prodromal stage: The classic symptoms for this stage are nausea, vomiting, anorexia and possibly diarrhea, which occur from minutes to days following exposure. The symptoms may for minutes up to several days. Latent stage: In this stage, the patient looks and feels generally healthy for a few hours or even up to a few weeks. Clinical stage: In this stage, the symptoms depend on the specific syndrome and last from hours up to several months. Recovery or death: Most patients who do not recover will die within several months of exposure. The recovery process lasts from several weeks up to two years. […] Radiation sickness results from acute radiation exposure to the skin. Usually caused exposure to beta radiation or X- rays. Basal cell layer of the skin is damaged by radiation, inflammation, erythema, and dry or moist desquamation can occur. Large skin doses can cause permanent hair loss, damaged sebaceous and sweat glands, atrophy, fibrosis, ulceration or necrosis of the exposed tissue.

• #57 CBRNE – Radiation Emergencies: Overview, Terminology, Biologic Effects of Ionizing Radiation

  https://emedicine.medscape.com/article/834015-reference

  Late toxicities, such as cataract formation and cancer, may appear months or years following an exposure. Other delayed effects are seen in organs with slowly dividing or quiescent, terminally differentiated cells such as the central nervous system, kidneys, and liver. Many of these late radiation effects are attributable to a combination of parenchymal cell death and microvascular disease. […] The acute radiation syndrome (ARS) occurs after whole-body exposure to a large dose of ionizing radiation. This syndrome includes a number of characteristic signs and symptoms whose severity depends on magnitude of dose and duration of exposure. ARS, by definition, does not occur at doses less than 1 Gy and is uniformly fatal at doses greater than 8 Gy. […] Acute radiation syndrome (ARS) has been described according to progression of illness through 4 stages: (1) prodrome, (2) clinical latency, (3) manifest illness, and (4) recovery or death. The prodromal symptoms occur shortly after irradiation, with the dose of exposure determining severity, duration, and onset.

• #58 Acute Radiation Syndrome: Information for Clinicians | Radiation Emergencies | CDC

  https://www.cdc.gov/radiation-emergencies/hcp/clinical-guidance/ars.html

  The dose must have been delivered in a short time (usually a matter of minutes). […] The primary cause of death is the destruction of the bone marrow, resulting in infection and hemorrhage. […] Destructive and irreparable changes in the GI tract and bone marrow usually cause infection, dehydration, and electrolyte imbalance. […] Death likely is due to collapse of the circulatory system as well as increased pressure in the confining cranial vault as the result of increased fluid content caused by edema, vasculitis, and meningitis. […] The classic symptoms for this stage are nausea, vomiting, as well as anorexia and possibly diarrhea (depending on dose), which occur from minutes to days following exposure. […] When the basal cell layer of the skin is damaged by radiation, inflammation, erythema, and dry or moist desquamation can occur. […] In most cases, healing occurs by regenerative means. However, very large skin doses can cause permanent hair loss, damaged sebaceous and sweat glands, atrophy, fibrosis, decreased or increased skin pigmentation, and ulceration or necrosis of the exposed tissue.

• #59 Acute radiation syndrome | PPT

  https://www.slideshare.net/DrAyushGarg/acute-radiation-syndrome-62265649

  Early radiation responses are described as deterministic. Deterministic radiation responses are those that exhibit increasing severity with increasing radiation dose. Furthermore, there is usually a dose threshold. […] ARS manifests itself in four major response stages: Prodromal (initial stage) Latent period Manifest illness Recovery. […] The severity of the symptoms is dose-related; the higher the dose, the more severe the symptoms. […] The LD50 is the dose necessary to kill 50% of the exposed population. The LD50/60 is the dose necessary to kill 50% of the exposed population in 60 days. […] The length of time involved for this stage to run its course may be hours or a few days. […] The prodromal syndrome varies in time of onset, severity, and duration. At doses close to the dose that would be lethal to 50% of the population (LD50), the principal symptoms of the prodromal syndrome are anorexia, nausea, vomiting, and easy fatigability. Immediate diarrhoea, fever, or hypotension indicate a supralethal exposure.

• #60 Treatment of acute radiation injuries | Tidsskrift for Den norske legeforening

  https://tidsskriftet.no/en/2013/10/treatment-acute-radiation-injuries

  Acute radiation syndrome is a clinical condition occurring when the entire body or large parts of it have been exposed to a dose of ionising radiation equal to 1 Gy or more. The most frequent cause will be external irradiation, but one case resulting from internal contamination is also known: Alexander Litvinenko developed acute radiation syndrome after having been poisoned with polonium mixed into a cup of tea. […] Acute radiation syndrome is a well-defined disease entity that develops through multiple clinical stages in a dynamic process. The disease manifests itself initially through so-called prodromal symptoms, mainly nausea and vomiting, as well as stomach pains, diarrhoea and other symptoms. The prodromal symptoms are reversible, and are assumed to be caused by an excitation of the autonomic nervous system.

• #61 Acute radiation syndrome | PPT

  https://www.slideshare.net/DrAyushGarg/acute-radiation-syndrome-62265649

  Early radiation responses are described as deterministic. Deterministic radiation responses are those that exhibit increasing severity with increasing radiation dose. Furthermore, there is usually a dose threshold. […] ARS manifests itself in four major response stages: Prodromal (initial stage) Latent period Manifest illness Recovery. […] The severity of the symptoms is dose-related; the higher the dose, the more severe the symptoms. […] The LD50 is the dose necessary to kill 50% of the exposed population. The LD50/60 is the dose necessary to kill 50% of the exposed population in 60 days. […] The length of time involved for this stage to run its course may be hours or a few days. […] The prodromal syndrome varies in time of onset, severity, and duration. At doses close to the dose that would be lethal to 50% of the population (LD50), the principal symptoms of the prodromal syndrome are anorexia, nausea, vomiting, and easy fatigability. Immediate diarrhoea, fever, or hypotension indicate a supralethal exposure.

• #62 Radiation sickness | PPT

  https://www.slideshare.net/slideshow/radiation-sickness-176759491/176759491

  The four stages of ARS are: Prodromal stage: The classic symptoms for this stage are nausea, vomiting, anorexia and possibly diarrhea, which occur from minutes to days following exposure. The symptoms may for minutes up to several days. Latent stage: In this stage, the patient looks and feels generally healthy for a few hours or even up to a few weeks. Clinical stage: In this stage, the symptoms depend on the specific syndrome and last from hours up to several months. Recovery or death: Most patients who do not recover will die within several months of exposure. The recovery process lasts from several weeks up to two years. […] Radiation sickness results from acute radiation exposure to the skin. Usually caused exposure to beta radiation or X- rays. Basal cell layer of the skin is damaged by radiation, inflammation, erythema, and dry or moist desquamation can occur. Large skin doses can cause permanent hair loss, damaged sebaceous and sweat glands, atrophy, fibrosis, ulceration or necrosis of the exposed tissue.

• #63 Acute radiation syndrome | PPT

  https://www.slideshare.net/DrAyushGarg/acute-radiation-syndrome-62265649

  Early radiation responses are described as deterministic. Deterministic radiation responses are those that exhibit increasing severity with increasing radiation dose. Furthermore, there is usually a dose threshold. […] ARS manifests itself in four major response stages: Prodromal (initial stage) Latent period Manifest illness Recovery. […] The severity of the symptoms is dose-related; the higher the dose, the more severe the symptoms. […] The LD50 is the dose necessary to kill 50% of the exposed population. The LD50/60 is the dose necessary to kill 50% of the exposed population in 60 days. […] The length of time involved for this stage to run its course may be hours or a few days. […] The prodromal syndrome varies in time of onset, severity, and duration. At doses close to the dose that would be lethal to 50% of the population (LD50), the principal symptoms of the prodromal syndrome are anorexia, nausea, vomiting, and easy fatigability. Immediate diarrhoea, fever, or hypotension indicate a supralethal exposure.

• #64 Radiation sickness | PPT

  https://www.slideshare.net/slideshow/radiation-sickness-176759491/176759491

  The four stages of ARS are: Prodromal stage: The classic symptoms for this stage are nausea, vomiting, anorexia and possibly diarrhea, which occur from minutes to days following exposure. The symptoms may for minutes up to several days. Latent stage: In this stage, the patient looks and feels generally healthy for a few hours or even up to a few weeks. Clinical stage: In this stage, the symptoms depend on the specific syndrome and last from hours up to several months. Recovery or death: Most patients who do not recover will die within several months of exposure. The recovery process lasts from several weeks up to two years. […] Radiation sickness results from acute radiation exposure to the skin. Usually caused exposure to beta radiation or X- rays. Basal cell layer of the skin is damaged by radiation, inflammation, erythema, and dry or moist desquamation can occur. Large skin doses can cause permanent hair loss, damaged sebaceous and sweat glands, atrophy, fibrosis, ulceration or necrosis of the exposed tissue.

• #65 Acute radiation syndrome | PPT

  https://www.slideshare.net/DrAyushGarg/acute-radiation-syndrome-62265649

  The gastrointestinal syndrome results from a total-body exposure to about 10 Gy (1,000 rad). Death occurs in about 5 to 10 days in humans because of depopulation of the epithelial lining of the gastrointestinal tract. […] The hematopoietic syndrome results from total-body exposure to 2.5 to 5 Gy (250-500 rad). The radiation sterilizes some or all of the mitotically active precursor cells. Symptoms result from lack of circulating blood elements 3 or more weeks later. […] The LD50 for humans is about 3 to 4 Gy (300-400 rad) for young adults without medical intervention. It may be less for the very young or the old. […] Some people who would otherwise die from the hematopoietic syndrome may be saved by antibiotics, platelet infusions, or bone-marrow transplants. […] The dose window over which bone-marrow transplants may be useful is narrow, namely, 8 to 10 Gy (800-1,000 rad).

• #66 Radiation – Health Effects, Exposure, Protection | Britannica

  https://www.britannica.com/science/radiation/Radiation-sickness

  The signs and symptoms resulting from intensive irradiation of a large portion of the bone marrow or gastrointestinal tract constitute a clinical picture known as radiation sickness, or the acute radiation syndrome. Early manifestations of this condition typically include loss of appetite, nausea, and vomiting within the first few hours after irradiation, followed by a symptom-free interval that lasts until the main phase of the illness. […] The main phase of the intestinal form of the illness typically begins two to three days after irradiation, with abdominal pain, fever, and diarrhea, which progress rapidly in severity and lead within several days to dehydration, prostration, and a fatal, shocklike state. The main phase of the hematopoietic form of the illness characteristically begins in the second or third week after irradiation, with fever, weakness, infection, and hemorrhage. If damage to the bone marrow is severe, death from overwhelming infection or hemorrhage may ensue four to six weeks after exposure unless corrected by transplantation of compatible unirradiated bone marrow cells.

• #67 Radiation – Health Effects, Exposure, Protection | Britannica

  https://www.britannica.com/science/radiation/Radiation-sickness

  The signs and symptoms resulting from intensive irradiation of a large portion of the bone marrow or gastrointestinal tract constitute a clinical picture known as radiation sickness, or the acute radiation syndrome. Early manifestations of this condition typically include loss of appetite, nausea, and vomiting within the first few hours after irradiation, followed by a symptom-free interval that lasts until the main phase of the illness. […] The main phase of the intestinal form of the illness typically begins two to three days after irradiation, with abdominal pain, fever, and diarrhea, which progress rapidly in severity and lead within several days to dehydration, prostration, and a fatal, shocklike state. The main phase of the hematopoietic form of the illness characteristically begins in the second or third week after irradiation, with fever, weakness, infection, and hemorrhage. If damage to the bone marrow is severe, death from overwhelming infection or hemorrhage may ensue four to six weeks after exposure unless corrected by transplantation of compatible unirradiated bone marrow cells.

• #68 Acute radiation syndrome | PPT

  https://www.slideshare.net/DrAyushGarg/acute-radiation-syndrome-62265649

  The gastrointestinal syndrome results from a total-body exposure to about 10 Gy (1,000 rad). Death occurs in about 5 to 10 days in humans because of depopulation of the epithelial lining of the gastrointestinal tract. […] The hematopoietic syndrome results from total-body exposure to 2.5 to 5 Gy (250-500 rad). The radiation sterilizes some or all of the mitotically active precursor cells. Symptoms result from lack of circulating blood elements 3 or more weeks later. […] The LD50 for humans is about 3 to 4 Gy (300-400 rad) for young adults without medical intervention. It may be less for the very young or the old. […] Some people who would otherwise die from the hematopoietic syndrome may be saved by antibiotics, platelet infusions, or bone-marrow transplants. […] The dose window over which bone-marrow transplants may be useful is narrow, namely, 8 to 10 Gy (800-1,000 rad).

• #69 Radiation – Health Effects, Exposure, Protection | Britannica

  https://www.britannica.com/science/radiation/Radiation-sickness

  The higher the dose received, the sooner and more profound are the radiation effects. Following a single dose of more than 5 Gy to the whole body, survival is improbable. A dose of 50 Gy or more to the head may cause immediate and discernible effects on the central nervous system, followed by intermittent stupor and incoherence alternating with hyperexcitability, epileptiform seizures, and death within several days. […] The blood-forming tissues are profoundly injured, and the white blood cell count may decrease within 15-30 days from about 8,000 per cubic millimetre to as low as 200. As a result of these effects, the body loses its defenses against microbial infection, and the mucous membranes lining the gastrointestinal tract may become inflamed. Furthermore, internal or external bleeding may occur because of a reduction in blood platelets.

• #70 Radiation sickness | PPT

  https://www.slideshare.net/slideshow/radiation-sickness-176759491/176759491

  The four stages of ARS are: Prodromal stage: The classic symptoms for this stage are nausea, vomiting, anorexia and possibly diarrhea, which occur from minutes to days following exposure. The symptoms may for minutes up to several days. Latent stage: In this stage, the patient looks and feels generally healthy for a few hours or even up to a few weeks. Clinical stage: In this stage, the symptoms depend on the specific syndrome and last from hours up to several months. Recovery or death: Most patients who do not recover will die within several months of exposure. The recovery process lasts from several weeks up to two years. […] Radiation sickness results from acute radiation exposure to the skin. Usually caused exposure to beta radiation or X- rays. Basal cell layer of the skin is damaged by radiation, inflammation, erythema, and dry or moist desquamation can occur. Large skin doses can cause permanent hair loss, damaged sebaceous and sweat glands, atrophy, fibrosis, ulceration or necrosis of the exposed tissue.

• #71 Clinical manifestations, evaluation, and diagnosis of acute radiation exposure – UpToDate

  https://www.uptodate.com/contents/clinical-manifestations-evaluation-and-diagnosis-of-acute-radiation-exposure

  Ionizing radiation can damage macromolecules (eg, DNA, RNA, proteins) and cellular components (eg, plasma membrane). Radiation effects can be direct (eg, single- or double-strand DNA breaks) or indirect (by interacting with water or other molecules to produce free radicals). […] Ionizing radiation has predictable dose- and time-dependent effects on hematopoiesis that are manifest as cytopenias (ie, neutropenia, lymphopenia, anemia, and thrombocytopenia) with resultant clinical consequences, including infections, weakness, and bleeding. […] The threshold whole-body dose for ARS in adults is approximately 1 Gy (100 rad); lower doses are not expected to cause clinically apparent ARS. A whole-body dose of 4.5 Gy is lethal to 50 percent of exposed persons (LD50) and a dose of ≥10 Gy is typically associated with 100 percent mortality.

• #72 Radiation sickness – UF Health

  https://ufhealth.org/conditions-and-treatments/radiation-sickness

  Total body exposure of 50 to100 roentgens/rad or 0.5 to1 Gray unit (Gy), equal to 500 to1,000 mSv causes radiation sickness. […] Total body exposure of 400 roentgens/rad (or 4 Gy) causes radiation sickness and death in half of the individuals who are exposed. […] 100,000 roentgens/rad (1,000 Gy) causes almost immediate unconsciousness and death within an hour.

• #73 Radiation sickness Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/injury/radiation-sickness

  Total body exposure of 50 to 100 roentgens/rad or 0.5 to 1 Gray unit (Gy), equal to 500 to 1,000 mSv causes radiation sickness. […] Total body exposure of 400 roentgens/rad (or 4 Gy) causes radiation sickness and death in half of the individuals who are exposed. […] 100,000 roentgens/rad (1,000 Gy) causes almost immediate unconsciousness and death within an hour.

• #74 Acute Radiation Syndrome: Information for Clinicians | Radiation Emergencies | CDC

  https://www.cdc.gov/radiation-emergencies/hcp/clinical-guidance/ars.html

  The dose must have been delivered in a short time (usually a matter of minutes). […] The primary cause of death is the destruction of the bone marrow, resulting in infection and hemorrhage. […] Destructive and irreparable changes in the GI tract and bone marrow usually cause infection, dehydration, and electrolyte imbalance. […] Death likely is due to collapse of the circulatory system as well as increased pressure in the confining cranial vault as the result of increased fluid content caused by edema, vasculitis, and meningitis. […] The classic symptoms for this stage are nausea, vomiting, as well as anorexia and possibly diarrhea (depending on dose), which occur from minutes to days following exposure. […] When the basal cell layer of the skin is damaged by radiation, inflammation, erythema, and dry or moist desquamation can occur. […] In most cases, healing occurs by regenerative means. However, very large skin doses can cause permanent hair loss, damaged sebaceous and sweat glands, atrophy, fibrosis, decreased or increased skin pigmentation, and ulceration or necrosis of the exposed tissue.

• #75 Radiation Sickness (Acute Radiation Syndrome)

  https://my.clevelandclinic.org/health/diseases/24328-radiation-sickness

  Radiation sickness (acute radiation syndrome) or radiation poisoning is a life-threatening condition that results from significant exposure to ionizing radiation. Its severity depends on: […] Radiation sickness is generally associated with acute (sudden and severe) exposure, like from a nuclear power plant accident. […] Radiation sickness (acute radiation syndrome) can occur after direct exposure or contamination by high doses of radioactive materials. […] But large doses cause cell death. […] A nuclear blast, radiation accidents and fallout from nuclear weapons testing can result in direct exposure. […] Symptoms may begin right after exposure or over the next few days, weeks or months. […] Each acute radiation syndrome (ARS) has distinct stages. […] Radiation sickness is often fatal. The time to death decreases as the dose of radiation increases. […] With survivors, long-term complications may occur. Survivors have an increased likelihood of radiation-induced cancer, including leukemia and thyroid cancer.

• #76 CBRNE – Radiation Emergencies: Overview, Terminology, Biologic Effects of Ionizing Radiation

  https://emedicine.medscape.com/article/834015-reference

  Late toxicities, such as cataract formation and cancer, may appear months or years following an exposure. Other delayed effects are seen in organs with slowly dividing or quiescent, terminally differentiated cells such as the central nervous system, kidneys, and liver. Many of these late radiation effects are attributable to a combination of parenchymal cell death and microvascular disease. […] The acute radiation syndrome (ARS) occurs after whole-body exposure to a large dose of ionizing radiation. This syndrome includes a number of characteristic signs and symptoms whose severity depends on magnitude of dose and duration of exposure. ARS, by definition, does not occur at doses less than 1 Gy and is uniformly fatal at doses greater than 8 Gy. […] Acute radiation syndrome (ARS) has been described according to progression of illness through 4 stages: (1) prodrome, (2) clinical latency, (3) manifest illness, and (4) recovery or death. The prodromal symptoms occur shortly after irradiation, with the dose of exposure determining severity, duration, and onset.

• #77 Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

  https://www.e-roj.org/journal/view.php?doi=10.3857/roj.2014.32.3.103

  Classically, normal tissue injury following high doses of radiation is thought to result from either depletion of parenchymal and/or vascular endothelial cells and attempts have been made to determine whether parenchymal or endothelial progenitors cells are the primary targets responsible for the tissue damage. […] More recent molecular and cellular studies suggest that dynamic secondary reactive processes in response to vascular endothelial cell and tissue stem and progenitor cell death leads to much greater cell loss, tissue damage, fibrosis, necrosis, and functional deficits. […] Excessive Generation of ROS Following Radiation […] Excessive Production of Cytokines and Chemokines […] Among the numerous pro-inflammatory cytokines and chemokines that are excessively produced immediately following radiation exposure, interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF)-, and transforming growth factor (TGF)- are major cytokines involved in the response of skin, lung, and brain.

• #78 The Microbiome and Radiation Induced-Bowel Injury: Evidence for Potential Mechanistic Role in Disease Pathogenesis

  https://www.mdpi.com/2072-6643/10/10/1405

  The overall acute consequence of radiation to the bowel is reduced tight junction integrity, the death of crypt epithelial cells, as well as those higher up the villi, depending on the intensity of the radiation. […] The majority of acute symptoms subside within a few weeks of completion of radiotherapy as the stem cells regenerate to reform the protective epithelial barrier. […] An increase in the expression of TGF-β1 which is a potent profibrogenic cytokine, is seen in epithelial cells, lamina propria, submucosa, subserosa, and smooth muscle cells soon after radiation. […] The chronic phase of enteropathy is characterized by chronic inflammation, fibrosis, progressive occluding vasculitis, ischemia, and dysmotility. […] The mechanism by which alteration in the gut microbiome affects radiation-induced bowel injury is anticipated to be extremely complex, with dynamic changes in microbial communities interacting with various components of enteric systems, rather than a consequence of a single compound.

• #79 Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

  https://www.e-roj.org/journal/view.php?doi=10.3857/roj.2014.32.3.103

  TGF- is considered to play a central role in mediating radiation-induced tissue fibrosis (skin, lung). […] The cascade of events leading to white matter necrosis is initiated by a gradual depletion of vascular endothelial cells which form the BBB. […] Chronic late effects of lung injury develop from dynamic interactions involving excessive ROS production, inflammatory cytokines and infiltration of bone marrow-derived stem and progenitors cells into the injured tissue.

• #80 Radiation-induced liver disease: current understanding and future perspectives | Experimental & Molecular Medicine

  https://www.nature.com/articles/emm201785

  RILD occurs as an acute response during or within a few weeks of RT or as a late-response months to years after RT. […] The early effects of irradiation include DNA damage, oxidative stress and reactive oxygen species production leading to hepatocellular apoptosis and acute inflammatory responses in irradiated regions. […] Although HCs are considered more radioresistant than nonparenchymal cells, the radiation-induced release of TNF- by KCs increases the susceptibility of HCs to radiation-induced apoptosis and ultimately induces hepatocellular death. […] The activation of HSCs is a key cellular event underlying hepatic fibrosis. […] This HSC activation is also suggested to be an essential process in RILD development because these cells are highly radiosensitive and accumulate in the livers of patients with RILD.

• #81 The Microbiome and Radiation Induced-Bowel Injury: Evidence for Potential Mechanistic Role in Disease Pathogenesis

  https://www.mdpi.com/2072-6643/10/10/1405

  The overall acute consequence of radiation to the bowel is reduced tight junction integrity, the death of crypt epithelial cells, as well as those higher up the villi, depending on the intensity of the radiation. […] The majority of acute symptoms subside within a few weeks of completion of radiotherapy as the stem cells regenerate to reform the protective epithelial barrier. […] An increase in the expression of TGF-β1 which is a potent profibrogenic cytokine, is seen in epithelial cells, lamina propria, submucosa, subserosa, and smooth muscle cells soon after radiation. […] The chronic phase of enteropathy is characterized by chronic inflammation, fibrosis, progressive occluding vasculitis, ischemia, and dysmotility. […] The mechanism by which alteration in the gut microbiome affects radiation-induced bowel injury is anticipated to be extremely complex, with dynamic changes in microbial communities interacting with various components of enteric systems, rather than a consequence of a single compound.

• #82 Radiation Sickness (Acute Radiation Syndrome)

  https://my.clevelandclinic.org/health/diseases/24328-radiation-sickness

  Radiation sickness (acute radiation syndrome) or radiation poisoning is a life-threatening condition that results from significant exposure to ionizing radiation. Its severity depends on: […] Radiation sickness is generally associated with acute (sudden and severe) exposure, like from a nuclear power plant accident. […] Radiation sickness (acute radiation syndrome) can occur after direct exposure or contamination by high doses of radioactive materials. […] But large doses cause cell death. […] A nuclear blast, radiation accidents and fallout from nuclear weapons testing can result in direct exposure. […] Symptoms may begin right after exposure or over the next few days, weeks or months. […] Each acute radiation syndrome (ARS) has distinct stages. […] Radiation sickness is often fatal. The time to death decreases as the dose of radiation increases. […] With survivors, long-term complications may occur. Survivors have an increased likelihood of radiation-induced cancer, including leukemia and thyroid cancer.

• #83 Radiation Health Effects | US EPA

  https://www.epa.gov/radiation/radiation-health-effects

  These studies show that radiation exposure increases the chance of getting cancer, and the risk increases as the dose increases: the higher the dose, the greater the risk. […] Conversely, cancer risk from radiation exposure declines as the dose falls: the lower the dose, the lower the risk. […] The use of the LNT model for radiation protection purposes has been repeatedly recommended by authoritative scientific advisory bodies, including the National Academy of Sciences and the National Council on Radiation Protection and Measurements. […] There is evidence to support LNT from laboratory data and from studies of cancer in people exposed to radiation.

• #84 Molecular Pathogenesis of Radiation-Induced Cell Toxicity in Stem Cells

  https://www.mdpi.com/1422-0067/18/12/2749

  The genetic and epigenetic instability of these cells may result in the accumulation of mutations to gain self-renewal and tumorigenic abilities. […] It is therefore important to develop new diagnostic and therapeutic techniques for predicting responses to cancer treatment and overcoming radiation-related toxicity.

• #85 Radiation Health Effects | US EPA

  https://www.epa.gov/radiation/radiation-health-effects

  These studies show that radiation exposure increases the chance of getting cancer, and the risk increases as the dose increases: the higher the dose, the greater the risk. […] Conversely, cancer risk from radiation exposure declines as the dose falls: the lower the dose, the lower the risk. […] The use of the LNT model for radiation protection purposes has been repeatedly recommended by authoritative scientific advisory bodies, including the National Academy of Sciences and the National Council on Radiation Protection and Measurements. […] There is evidence to support LNT from laboratory data and from studies of cancer in people exposed to radiation.

• #86 Radiation Injury – Injuries and Poisoning – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/injuries-and-poisoning/radiation-injury/radiation-injury

  The hematopoietic syndrome is caused by the effects of radiation on the bone marrow, spleen, and lymph nodes—the primary sites of blood cell production (hematopoiesis). […] The gastrointestinal syndrome is due to the effects of radiation on the cells lining the digestive tract. […] The cerebrovascular syndrome occurs when the total dose of radiation exceeds 30 Gy. […] High accumulated doses of radiation to the spinal cord can cause catastrophic damage, leading to paralysis, incontinence, and loss of sensation. […] Treatment of serious, life-threatening injuries first. […] Irradiation has no emergency treatment, but doctors closely monitor people for the development of the various syndromes and treat the symptoms as they arise. […] The outcome depends on the radiation dose, dose rate (how quickly the exposure occurs), and the parts of the body that are affected. Other factors include people’s state of health and whether they receive medical care.

• #87 Pathology and Pathogenesis of Radiation Bowel Disease: Histopathological Appraisal in the Clinical Setting – European Medical Journal

  https://www.emjreviews.com/gastroenterology/article/pathology-and-pathogenesis-of-radiation-bowel-disease-histopathological-appraisal-in-the-clinical-setting/

  The damaging effect of radiotherapy is most potent against tissues with high cellular turnover, making it ideal for treating rapidly proliferating tumour cells. […] Importantly, during the acute phase, the vasculature appears normal. The vascular phase follows the epithelial phase, which is characterised by telangiectasia of capillaries and post-capillary venules, fibrin deposition, subendothelial oedema, and platelet thrombi formation that can cause rectal bleeding. […] The reversibility of the vascular phase morphological changes is unclear; however, the stromal phase, which includes mesenchymal and stromal fibrosis, is irreversible. […] Despite these distinctions, the bowel has a limited array of modifications in response to damage. In fact, under a microscope the quiescent phase of inflammatory bowel disease looks the same as chronic RBD.

• #88 Radiation-induced heart disease: a review of classification, mechanism and prevention

  https://www.ijbs.com/v15p2128.htm

  Radiation-induced endothelial cell injury is deemed to be the primary and fundamental cause of myocardial injury. […] The above inflammatory factors can not only mediate the production of inflammation, but also promote the proliferation of endothelial cells and fibroblasts, the increase of collagen deposition can cause the thickening of vessel walls and the stenosis of lumen. […] Myocardial ischemia and hypoxia, inflammatory responses, collagen deposition, and proliferation of endothelial cells and fibroblasts lead to tissue remodeling, cardiac fibrosis, and atherosclerosis, and these changes are the primary endpoints of RIHD. […] Although the effect of radiation on the heart has been clear in pre-clinical trials, the underlying mechanism of RIHD gradual progression from no clinical manifestations in the early stage to chronic heart disease in the later stage is not fully understood.

• #89 CBRNE – Radiation Emergencies: Overview, Terminology, Biologic Effects of Ionizing Radiation

  https://emedicine.medscape.com/article/834015-reference

  Late toxicities, such as cataract formation and cancer, may appear months or years following an exposure. Other delayed effects are seen in organs with slowly dividing or quiescent, terminally differentiated cells such as the central nervous system, kidneys, and liver. Many of these late radiation effects are attributable to a combination of parenchymal cell death and microvascular disease. […] The acute radiation syndrome (ARS) occurs after whole-body exposure to a large dose of ionizing radiation. This syndrome includes a number of characteristic signs and symptoms whose severity depends on magnitude of dose and duration of exposure. ARS, by definition, does not occur at doses less than 1 Gy and is uniformly fatal at doses greater than 8 Gy. […] Acute radiation syndrome (ARS) has been described according to progression of illness through 4 stages: (1) prodrome, (2) clinical latency, (3) manifest illness, and (4) recovery or death. The prodromal symptoms occur shortly after irradiation, with the dose of exposure determining severity, duration, and onset.

• #90 Radiation Exposure and Contamination – Injuries; Poisoning – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/injuries-poisoning/radiation-exposure-and-contamination/radiation-exposure-and-contamination

  Late reactions (eg, in the lungs, kidneys, and brain) involve complex and dynamic interactions between multiple cell types in the tissues and organs and include infiltrating immune cells; production of cytokines and growth factors; often in persistent, cyclic cascades; and chronic oxidative stress. […] The severity of radiation injury depends on the dose and the length of time over which it is delivered. A high, single, rapid dose is more damaging than the same dose given over weeks or months. […] Other factors can increase the sensitivity to radiation injury. Children are more susceptible to radiation injury because they have a higher rate of cellular proliferation. […] The chance of developing cancer due to commonly encountered doses (ie, from background radiation and typical imaging tests) is much less and may be zero.

• #91 The Microbiome and Radiation Induced-Bowel Injury: Evidence for Potential Mechanistic Role in Disease Pathogenesis

  https://www.mdpi.com/2072-6643/10/10/1405

  Current evidence suggests that the pathophysiology of acute and particularly chronic radiation-induced bowel injury is caused by a dynamic interplay of change in gut microbiota, epithelial cell damage and repair, endothelial injury and remodeling, fibrogenesis, alterations of the enteric nervous system, as well as inflammatory response orchestrated by the innate and adaptive immune system.

• #92 Radiobiology of the acute radiation syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3863296/

  Acute radiation syndrome or acute radiation sickness is classically subdivided into three subsyndromes: the hematopoietic, gastrointestinal and neurovascular syndrome but many other tissues can be damaged. […] Classical pathophysiology explain the failure of each of these organs and the timing of appearance of their signs and symptoms due to radiation-induced cytocidal effects of a great number of parenchymal cells of hierarchically organized tissues. […] Radiation-induced multi-organ involvement is thought to be due to radiation-induced systemic inflammatory response mediated by released pro-inflammatory cytokines. […] Classical radiobiology explain the failure of each of these organs by radiation-induced death (cytocidal effects) of a great number of parenchymal cells (target cell theory) but today we know that radiation not only cause lethal effects but also functional and indirect effects in many cells (multi-cellular target theory).

• #93 Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

  https://www.e-roj.org/journal/view.php?doi=10.3857/roj.2014.32.3.103

  To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. […] The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. […] Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. […] Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues.

• #94 Exploration of radiation-induced lung injury, from mechanism to treatment: a narrative review – Yan – Translational Lung Cancer Research

  https://tlcr.amegroups.org/article/view/61434/html

  The pathological change of RILI is mediated by a series of cells and cytokines. […] Radiation induces DNA damage, and the generation of reactive oxygen stimulates the activation of inflammatory pathways. […] Direct damage to epithelial alveolar and endothelial cells leads to pro-inflammatory and pro-fibroblast activity. […] The release of a variety of cytokines drives the action of macrophages and the differentiation of fibroblasts. […] TGF- plays a key role in this process, and IFN-, macrophages, and PGE2 have a positive impact in inhibiting lung fibrosis. […] However, IL-4 and IL-13 secreted by Th2 cells exert a contrary effect. […] Fibroblasts proliferate and differentiate to drive collagen synthesis and ECM deposition under the influence of TGF-, IL-4, IL-13, IFN-, PGE2, and others. […] A variety of chemokines promote the development of RILI.

• #95 Acute radiation syndrome caused by accidental radiation exposure – therapeutic principles | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-126

  Pathophysiological aspects of radiation-induced MOI include systemic inflammatory response syndrome (SIRS) and consequences of cell loss due to radiation damage. Therapeutic efforts are to be taken to stabilize the homoeostasis and to reconstitute the function of organs and organ systems. A new strategy would be an early therapeutic intervention in order to prevent MOF already in the stage of SIRS. The pathophysiological mechanisms behind this development are still poorly understood. […] The main specific therapeutic principles are replacement with blood products, the administration of cytokines like G-CSF and GM-CSF, and the transplantation of hematopoietic stem cells. […] In addition to hematopoietic syndrome, radiation-induced damage to the skin plays an important role in diagnostics and treatment of patients with ARS and eventually might trigger the development of multi-organ failure.

• #96 Mechanisms Involved in Chronic Radiation Exposure Effects: Pathogenesis of Chronic Radiation Syndrome | Radiology Key

  https://radiologykey.com/mechanisms-involved-in-chronic-radiation-exposure-effects-pathogenesis-of-chronic-radiation-syndrome/

  Chronic radiation syndrome is considered to be a system response of a human body as a unified whole to chronic radiation exposure. […] At the basis of such changes there are radiation-induced impairments in the regulatory systems. […] If the exposure dose for certain organs exceeds the threshold values, then, not only functional, but also organic changes develop (vascular impairments, dystrophy, fibrosis, RBM hypoplasia, etc.), and the CRS course acquires an irreversible character. […] It is assumed that the mechanism of radioadaptation is associated with a set of compensatory-reparative response at the cellular, organ, and organismic levels. […] Understanding of CRS pathogenesis is of not only theoretical interest but also practical, as peculiarities of CRS pathogenesis determine the strategy of complex pathogenetic therapy, the main principles of which are not yet formulated.

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