Radiation injury and countermeasures: ALOK SONI
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Radiation can be ionizing or non-ionizing, with ionizing radiation including alpha, beta, gamma, and neutron radiation capable of damaging cells. Radiation exposure is measured in units like the gray (Gy) and sievert (Sv) which account for both energy absorbed and biological effects. Radiation can directly damage DNA and indirectly generate reactive oxygen species, leading to acute effects above 1 Gy or chronic effects like cancer. Potential countermeasures include radioprotectors administered before exposure, mitigators after exposure, and therapeutics for symptoms. Promising agents include amifostine, 5-AED, G-CSF and HDAC inhibitors, but developing safe and effective countermeasures remains an ongoing challenge.
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Radiation injury and countermeasures: ALOK SONI
- 1. Alok Kumar SRF-Pharm. & Toxi. Radiation Injury and Countermeasures
- 2. Radiation, sources Introduction Direct and indirect, acute and chronic Mechanism of toxicity Radioprotector, mitigator, therapeutics Countermeasures . Conclusion A B C D
- 3. Radiation is the process by which energy is emitted as either particles or waves. Non-ionizing or ionizing: Non-ionizing radiation is longer wavelength/lower frequency lower energy. While ionizing radiation is short wavelength/high frequency higher energy Introduction ICRP Publication 103. Pergamon Press, Oxford, 2007
- 4. Ionizing Radiation: Alpha radiation (α) Beta radiation (β) Photon radiation (gamma [γ] and X-ray) Neutron radiation (n) ICRP Publication 103. Oxford, 2007
- 5. Radiation with sufficiently high energy can ionize atoms; that is to say it can knock electrons off atoms and create ions. Ionizing radiation includes the radiation that comes from both natural ()and man-made radioactive materials 82 % 18 %
- 6. Natural background radiation India Air passengers receive 5 microgray per hour from cosmic rays The total annual external dose from sources in soil and cosmic rays in Mumbai, Kolkata, Chennai, Delhi and Bangalore is 0.484, 0.81, 0.79, 0.70 and 0.825 mGy respectively. Parts of Kerala and Tamil Nadu are high background radiation areas (HBRA) because of the presence of large quantities of monazite in the soil. Karunagapally taluk in Kerala has radiation background upto 70000 micro Gy/yr. Bananas are a natural source of radioactive isotopes. Eating one banana = 1 BED = 0.1 μSv = 0.01 mrem Department of Atomic Energy, 2009
- 7. How is radiation measured ? Expousre: Measure of ionization produced by X or gama radiation in air Unit is Roentgen (R) Absorb dose unit: The absorb dose is the amount of energy absorb by tissue per unit mass Non SI- Radiation absorb dose (rad) SI- GRAY (Gy) Dose Equivalent: Measure of Biological effect of radiation Non SI- Roentgen equivalent man (rem) SI- Sievert (Sv) 1 Roentgen = 1 rad = 1 rem =10 mGy = 10 mSv Review of radiologic physics 2003
- 8. Radiation induced injury can occur in three way: External irradiation, contamination with radioactive material, and incorporation of these into body cells, tissues or organs. Severity of Injury: In general, the higher the dose, the more severe the early effects will be and the greater the possibility of delayed effects. Direct Interaction: Indirect Interaction: What happens in a cell when ionizing radiation interacts with it ? An Introduction to Radiobiology, 1998
- 9. Direct interaction Macromolecules (proteins or DNA) are hit by the ionizing radiation, which affects the cell as a whole, either killing the cell or mutating the DNA Actively dividing cells are more radiosensitive than nondividing cells : M phase, is the most radiosensitive Increased chromatin in cancer cells is why these cells, which have unusually high mitotic rates, are more radiosensitive than normal cells An Introduction to Radiobiology, 1998
- 10. Indirect interaction Excessive Generation of ROS Following Radiation: Free Radic Biol Med 2005
- 11. Excessive Production of Cytokines and Chemokines: immediately following radiation exposure: (IL-1), IL-6, (TNF)-α and transforming growth factor (TGF)-β are major cytokines involved. BMDC (mesenchymal stem cell, endothelial progenitor cell and myelomonocytic cell) recruited at radiated tissue by over expression of C-X-C Chemokines ligand 12 (CXCL-12), also known as stromal cell- derived factor-1 (SDF-1) and C-X-C Chemokines receptor type 4 (CXCR4) are responsible. Myelomonocytic cells (CD11b), are the predominant BMDC that localize to the irradiated tissues and it can negatively affect tissue by cytokines mediated inflammation. Radiat Oncol J 2014 Pathophysiology
- 12. Indirect or direct Radiat Oncol J 2014;
- 13. Biological effect of radiation DOSE–RESPONSE MODELS Linear no-threshold dose–response model :. For any known carcinogen at any level of exposure a linear no threshold dose–response model is used across all industries. This model states that any radiation exposure, no matter how small, can induce cancer. Linear threshold Dose Response: a known threshold below which no effects are seen. At the threshold level, effects are noticeable and increase linearly as the dose increases Nucl Med Technol 2017
- 14. Stochastic effects •They have no threshold dose •Independent of dose but probability increase with dose •Stochastic effects include radiation carcinogenesis and hereditary effects Non stochastic or deterministic effects •Related with certainty to known dose •Dose threshold exists •Severity is dose related Ind J Radiol Imag 2002 Biological effects of Radiation
- 15. Biological effect of radiation Acute Radiation Effects “Harmless” at background or diagnostic levels but is non stochastic at high-dose levels. >1 Gy exposure of gamma rays lead to Acute Radiation Syndrome (ARS) Chronic Radiation Effects •Chronic effects of ionizing radiation exposure are primarily stochastic. The chief concern is possible cancer induction (thyroid, bone, lung, and various other cancers) •Noncancerous effects are possible, such as cataract formation in the eye, Leukemia https://emergency.cdc.gov/radiation/pdf/arsphysicianfactsheet.pdf
- 17. 1945: (Japan) nuclear attack leads approximately 150,000 died instantly and thousand are still facing serious complications. Some 150,000 people, including 60,000 children, were affected by radioactive dust from the Chernobyl power plant accident, (report of European Parliament in 1992) Serious Radiation Disaster Fuku) WHO/IAEA/UNDP joint news release, 2005
- 18. Radiation countermeasure agents: Medical preparedness and countermeasures are critical security issues, not only for the individual but also for the nation as well. Radiation countermeasures Radioprotector Mitigator therapeutics i) Protect against both acute and chronic radiation damages; ii) be suitable for oral (p.o.) administration with rapid absorption and distribution throughout the body; iii) have no significant toxic side effects including behavioral; iv) be readily available and inexpensive; and v) be chemically stable for easy handling, transport and storage for field use. Ideal radiation countermeasure Expert Opin. Ther. Patents (2014
- 19. Radioprotector Radioprotectors are given prior to radiation exposure to prevent damage; hence they are helpful in planned radiation exposure like as in radiotherapy and first responder applications. 1. Amifostine 2. 5-AED/Neumune 3. G-CSF/Neupogen/Filgrastim 4. 2.3 γ-tocotrienol 5. 2.4 Genistein 6. Herbal Radioprotector • Podophyllum Hexandrum, • Hippophae Rhamnoides • Ocimum Sanctum
- 20. Amifostine: (WR 2721), a thiol, is a potent radioprotector that has been approved by USFDA for human application but only under strict medical supervision. 5-androstenediol (5-AED): It is a naturally occurring adrenal steroid hormone holding promise against hematological acute radiation syndrome as protector as well as mitigator. G-cSF/neupogen/Filgrastim: Granulocyte Colony Stimulating Factor (G-CSF) and Granulocyte Monocyte-Colony Stimulating Factor (GM-CSF) are likely to receive FDA approval. γ-tocotrienol: After promising radioprotective in the rodents, its efficacy in non- human primates (NHP) model is under evaluation. Genistein: (BIO 300) A phytoestrogen, has antioxidant activity modulate signal transduction pathway. Herbal compounds are also considered very safe and of high value as radiation countermeasure agents owing to various properties like antioxidant, immunomodulation activity etc Expert Opin. Ther. Patents 2014
- 21. Radiomitigators Required during unplanned and accidental radiation exposure. Radiomitigators are agents which are administered after radiation exposure to mitigate the effect of radiation 1. Sulforaphane 2. Diallyl sulphide 3. Epigallocatechin-3-gallate 4. Other Histone deacetylase inhibitors 5. ACE inhibitors 6. Melatonin Expert Opin. Ther. Patents (2014
- 22. HDAC inhibitor: Histone Deacetylase inhibitors (HDACi) are epigenetic modifiers involved in regulation of gene expression, differentiation, proliferation and apoptosis of cells. they increases histone acetylation thus increasing the accessibility of repair proteins to DNA and thereby enhancing DNA repair. Sulforaphane: Sulforaphane (SFN) is an isothiocynate dietary supplement present in cruciferous vegetables like broccoli, cabbage and cauliflower and shows anticancer activity. Diallyl Sulphide: Diallyl sulphide (DAS) is a naturally occurring organosulphur present in garlic. DAS exhibits radioprotective activity in liver, intestinal mucosa and hematopoietic injury Epigallocatechin-3-gallate: Green tea contains a which shows high anti-oxidant and anti-inflammatory activity and provide mitigation against radiation injury. Melatonin: Radioprotection with melatonin and melatonin analogs has been documented in a number of animal models. Expert Opin. Ther. Patents (2014
- 23. A therapeutic is an agent which is given after the appearance of physical symptoms of radiation exposure. 1. Infusion of Hematopoietic Stem Cells 2. Growth Factors 3. Recombinant GCSF/ Filgrastim 4. Recombinant Pegfilgrastim/Neulasta Therapeutics: Treating internal contamination Potassium Iodide (KI) Prussian Blue DTPA (Diethylenetriamine pentaacetate) Expert Opin. Ther. Patents (2014
- 28. Conclusion Radiation injury is a complex pathological syndrome that follows a typical clinical course characterized by excessively prolonged or incomplete healing. Development of a radiation countermeasure agent, whether protector, mitigator or therapeutic is a very complicated task with rare success. Therefore, there is a need of constant and holistic efforts by more and more researchers. Recent events in Japan as well as the nuclear weapons testing in North Korea, suggest increased potential and reality of a nuclear threat and radiological events.
Editor's Notes
- Radiation is generally classified ionizing or non-ionizing, based on whether it has enough energy to knock electrons off atoms that it interacts with, as well as being able to do lower energy damage such as breaking chemical bonds in molecules. Ionizing radiation, which is caused by unstable atoms giving off energy to reach a more stable state, is more of a health threat to humans because it involves changing the basic makeup of atoms in cells, and more specifically the DNA molecules inside of cells. It does, of course, take a very strong dose of radiation to substantially damage a cell’ s structure, as there can be trillions of atoms in a single Cell. Most non-ionizing radiation, such as radio and microwave energy , is considered harmful only to the extent of the amount of heat energy it transfers to whatever it hits. This is, in fact, the way that microwaves cook food. UV light is unique in that while it is non-ionizing, it does have the capacity to cause harmful effects similar to what ionizing radiation can create, such as an increased risk of cancer due to damage to DNA molecules
- Background radiation consists of three sources ; Cosmic radiation from the sun and stars. Terrestrial radiation from low levels of uranium, thorium, and their decay products in the soil, air and water. Internal radiation from radioactive potassium-40, carbon-14, lead-210, and other isotopes found inside our bodies Natural background radiation We are all exposed to ionizing radiation from natural sources at all times. Levels of natural or background radiation can vary greatly from one location to the other Main sources are: Cosmic rays Radioactivity in the Earth (U-238, Th-232 etc) High natural background areas Natural radioactivity in the body (K- 40, C-14) Radon progeny (largest exposure to public)
- The background radiations in certain parts of our country show high levels. Kerala with thorium in the sand has shown high background radiation levels. In fact Karunagapally taluk in Kerala has radiation background upto 70000 micro Gy/yr, primarily due to the thorium deposits. Such instances are also found in other parts of the world e.g. Ramsar, a city in Northern Iran, people have been receiving upto 260000 micro Sievert/yr dose due to natural radiation. Living in areas of such regions of high radiation however has not shown any increased instances of cancer risks as compared to people living in areas with normal background radiation. In our country, background natural radiation fields are measured by INDIAN ENVIRONMENTAL RADIATION MONITORING NETWORK (IERMON) by BARC, Department of Atomic Energy (DAE) which has several stations across the country and the readings of the radiation fields are available on-line in DAE. The data show that there is at least 10 % variation in the radiation fields on both the sides of average readings The third source of natural radiation is the naturally occurring isotopes mainly Tritium, Carbon-14 and Potassium-40 which enter our body through the food we eat, water we drink and the air we breathe. They eventually make their way into our food chain. Once ingested, they decay and give us an internal dose. Let us look at it with an illustration. A typical banana contains about half a gram of Potassium. The dose of radiation that a person absorbs by consuming one banana is defined as Banana Equivalent Dose (BED). One BED approximately works out to 0.08 micro Sievert, corresponding to nearly one-fourth of the annual dose absorbed by a person residing at the boundary of a Nuclear Power Plant. We live in a sea of radiation. In any city, an unsuspecting owner of a 0.1 acre backyard garden may not know that the top one metre of soil from his garden contains 11,200 kg of potassium, 1.28 kg which is of potassium- 40 (K-40, a radioactive isotope of potassium), 3.6 kg of thorium and one kg of uranium. These values may be higher or lower depending on the soil. Uranium and thorium decay through several radio-nuclides to lead, a stable element. The presence of radioactive nuclides does not pose any significant risk. There is an urgent need for the development of radiation countermeasure agents to ameliorate or reduce the morbidity and mortality caused due to radiation over exposures in planned and unplanned activities1. Total dose The total annual external dose from sources in soil and cosmic rays in Mumbai, Kolkata, Chennai, Delhi and Bengaluru is 0.484, 0.81, 0.79, 0.70 and 0.825 milligray respectively. Gray is a unit for absorbed dose; when the radiation energy imparted to a kg of material is one joule, it is called a gray. Since gray is very large, milligray (one thousandth of a gray), and microgray (one millionth of a gray), are commonly used. Cosmic rays come from outer space. Their intensity at a place depends on the altitude. Cosmic rays alone contribute 0.28 milligray at the first three cities as they are at sea level; the column of air helps to reduce their intensity. At high altitudes, the protection from the column of air is less. The cosmic ray contributions are higher at 0.31 milligray and 0.44 milligray respectively at Delhi and Bengaluru as these cities are at altitudes of 216 metre and 921 metre. Air passengers receive 5 microgray per hour from cosmic rays.
- The radioactivity of a substance, or how “active” it is radioactively , is measured in either curies (Ci) or Becquerel’ s (Bq). Both are measures of the number of decays per second, or how often an atom in a given sample will undergo radioactive decay and give off a particle or photon of radiation. The curie (1 Ci equals about 37 ,000,000,000 decays per second) is named after Marie and Pierre Curie, and is equal to roughly the activity of one gram of radium, which they studied. The Becquerel is the SI unit for radioactivity . One Bq equals one decay per second. The Bq is the SI unit, though the curie remains widely used throughout the US in both government and industry
- What happens in a cell when ionizing radiation interacts with it? There are really only 2 possibilities: direct interaction or indirect interaction in a cell. n direct interaction, a cell’s macromolecules (proteins or DNA) are hit by the ionizing radiation, which affects the cell as a whole, either killing the cell or mutating the DNA (2). There are many target and cell survival studies showing that it is harder to permanently destroy or break double-stranded DNA than single-stranded DNA. Although humans have 23 pairs of double-stranded chromosomes, some cells react as if they contain single-stranded, nonpaired chromosomes and are more radiosensitive. Many different types of direct hits can occur, and the type of damage that occurs determines whether the cell can repair itself. Generally, if a direct hit causes a complete break in the DNA or some other permanent damage, the cell dies immediately or will die eventually (5). However, humans have an abundance of cells, and somatic cellular reproduction (mitosis) is always occurring to replace cells that die. Therefore, it is only when this system of replacing cells falters that radiation effects are seen. This occurs at higher doses of radiation. Actively dividing cells are more radiosensitive than nondividing cells. There are 4 phases of mitosis: M phase, in which cells divide into two; G1 phase (gap 1), in which cells prepare for DNA replication; S phase, in which DNA doubles by replication; and G2 phase (gap 2), in which cells prepare for mitosis. Of these, M phase, in which the chromosomes are condensed and paired, is the most radiosensitive. More DNA is present in one area at this point in the cycle, which is why it is theorized that this is the most radiosensitive time. It is also thought that increased chromatin in cancer cells is why these cells, which have unusually high mitotic rates, are more radiosensitive than normal cells (6). The other type of interaction is indirect cellular interaction. Indirect interaction occurs when radiation energy is deposited in the cell and interacts with cellular water rather than with macromolecules within the cell. The reaction that occurs is hydrolysis of the water molecule, resulting in a hydrogen molecule and a hydroxyl (free radical) molecule. If the 2 hydroxyl molecules recombine, they form hydrogen peroxide, which is highly unstable in the cell. This will form a peroxide hydroxyl, which readily combines with some organic compound, which then combines in the cell to form an organic hydrogen peroxide molecule, which is stable. This may result in the loss of an essential enzyme in the cell, which could lead to cell death or a future mutation of the cell (Table 1) (5). Antioxidants, about which there has been much research and publicity, block hydroxyl (free radical) recombination into hydrogen peroxide, preventing stable organic hydrogen peroxide compounds from occurring. This is one way in which the body can defend itself from indirect radiation interactions on a cellular level and is one reason that antioxidants have received so much attention as a cancer prevention agent (7). After the dropping of the atomic bombs in Japan, experiments were carried out on various animals to determine the dose that would kill 50 percent of the experimental animal population within a set time period. Accident data on humans that were not treated indicate the lethal dose (LD) 50 was in the region of 350 rads to 450 rads.
- Actively dividing cells are more radiosensitive than nondividing cells. There are 4 phases of mitosis: M phase, in which cells divide into two; G1phase (gap 1), in which cells prepare for DNA replication; S phase, in which DNA doubles by replication; and G2 phase (gap 2), in which cells prepare for mitosis. Of these, M phase, in which the chromosomes are condensed and paired, is the most radiosensitive. More DNA is present in one area at this point in the cycle, which is why it is theorized that this is the most radiosensitive time. It is also thought that increased chromatin in cancer cells is why these cells, which have unusually high mitotic rat ares, are moreradiosensitive than normal cells (6).
- The other type of interaction is indirect cellular interaction. Indirect interaction occurs when radiation energy is deposited in the cell and interacts with cellular water rather than with macromolecules within the cell. The reaction that occurs is hydrolysis of the water molecule, resulting in a hydrogen molecule and a hydroxyl (free radical) molecule. If the 2 hydroxyl molecules recombine, they form hydrogen peroxide, which is highly unstable in the cell. This will form a peroxide hydroxyl, which readily combines with some organic compound, which then combines in the cell to form an organic hydrogen peroxide molecule, which is stable. This may result in the loss of an essential enzyme in the cell, which could lead to cell death or a future mutation of the cell (Table 1) (5). Antioxidants, about which there has been much research and publicity, block hydroxyl (free radical) recombination into hydrogen peroxide, preventing stable organic hydrogen peroxide compounds from occurring. This is one way in which the body can defend itself from indirect radiation interactions on a cellular level and is one reason that antioxidants have received so much attention as a cancer prevention agent
- Shortly after radiation exposure to the tissue and organs, a cascade of cytokines and chemokines is initiated and mediators released in the irradiated tissues perpetuate and augment the inflammatory response for long periods of time, leading to possible chronic inflammation and tissue injury (see Fig. 1). 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)-α , and transforming growth factor (TGF)-β are major cytokines involved in the response of skin, lung, and brain. Chemokines responsible for the recruitment of bone marrow-derived cells (BMDC) into the irradiated tissues include C-X-C chemokine ligand 12 (CXCL-12), also known as stromal cell-derived factor-1 (SDF-1) and C-X-C chemokine receptor type 4 (CXCR4). TGF-β is a multifunctional and pleiotropic cytokine affecting many cellular processes including epithelial cell growth, mesenchymal cell proliferation, and extracellular matrix production. Irradiation, even at low doses, is one of the few exogenous factors known to induce TGF-β activation [5] and TGF-β is considered to play a central role in mediating radiation-induced tissue fibrosis (skin, lung) [6]. Elevated levels of fibrosis after thoracic and abdominopelvic radiotherapy have been correlated with the levels of TGF-β [7]. Molecular mechanisms of TGF-β signaling involve binding of TGF-β to type I/II receptor complexes leading to activation of Smad proteins. It has been shown that activation of Smad3 downstream is critically involved in the development of radiation-induced fibrosis. Smad3 knockout mice exhibit reduced radiation skin damage, reduced inflammatory infiltrates, and increased rate of epithelialization relative to the wild-type control mice [8]. TNF-α is a multifunctional cytokine involved in both acute and chronic inflammation. It is produced primarily by activated macrophages, although it can be produced by other hematopoietic and non-hematopoietic cells as well. Large amounts of TNF-α , along with IL-1, are released in response to lipopolysaccharide and other bacterial products. In addition to their pro-inflammatory effects, both TNF-α and IL-1 also stimulate the secretion of matrix metalloproteinases (MMPs). MMPs are a family of secreted proteolytic enzymes that have the capacity to degrade the basal membrane and the extracellular matrix. A local increase in TNF-α concentration in conjunction with IL-1 produce the cardinal signs of acute skin reaction, where IL-1 appears to play a critical role in the inflammatory response [9]. Several TNF-α inhibitors (monoclonal antibodies or receptor fusion proteins) have been developed and are in clinical use for autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Pre-clinical studies with TNF-α inhibitors have also established that they significantly mitigate radiation-induced skin injury in mice [10,65]. Vascular endothelial growth factor (VEGF) is among the first growth factors upregulated during the pathogenesis associated with late delayed effects of brain injury. The upregulation of VEGF evolves gradually following brain irradiation and typically occurs several weeks prior to the development of overt tissue pathology [11]. The cascade of events leading to white matter necrosis is initiated by a gradual depletion of vascular endothelial cells which form the BBB. The reduction in endothelial cell number is not accompanied by a substantial decrease in vascular density, rather the endothelial cell density in the existing vasculature is reduced which gradually diminishes the integrity of BBB [12
- 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. Fig. 1 illustrates the dynamic interactions involving radiation-induced death of target cells, generation of reactive oxygen species (ROS) and subsequent secondary reactive pro-inflammatory processes and innate immune responses that are believed to contribute to selective cell loss, tissue damage, and functional deficits.
- Alternative relationships for cancer risk vs. radiation dose as extrapolate to low-dose exposures, given a known risk at a high dose: supra-linearity (A), linear (B), linear-quadratic (C) and hormesis, which implies a biologically beneficial effect at low dose (D). The excess risk for solid tumor formation in survivors of Nagasaki and Hiroshima bombings follows a dose response curve best described by a linear or linear-quadratic function. There is no statistically significant advantage to using the more complex linear-quadratic expression for estimating solid tumor risk. For leukemia data, however, a linear quadratic model is most appropriate. Only the linear and linear-quadratic functions are currently recognized by major risk assessment and management agencies. The figure below summarizes all potential functions offered to explain low dose exposures and cancer risk It is important to remember that for all dose–response models, the dose makes the poison. Perhaps this was best stated by Paracelsus, who is considered the father of toxicology: “All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy” (11). Generally, as the dose increases, response increases to a toxic point; in other words, anything in excess can be toxic. Radiation dose–response models vary depending on what is being analyzed. It is important to remember that there is evidence to suggest a possible threshold for radiation exposure that would favor the linear threshold dose–response model. Also, any dose–response model for radiation in the lower levels is extrapolated from what is known at high-dose levels. Thus, any lower-level response from radiation is only theorized, not proven. The only dose–response model accepted by the Nuclear Regulatory Commission is the linear no-threshold dose–response model, which suggests that any radiation exposure can lead to cancer induction.
- Stochastic means random in nature. There is a statistical accounting for all diseases that could be caused by any of several different xenobiotics or carcinogens; any random occurrence of a disease that cannot be attributed solely to radiation is stochastic. As far as cancer is concerned, it is extremely difficult to say whether a particular cancer is attributable to a specific exposure because most cancers have a 20-y latency period from exposure to manifestation. Therefore, chronic low-dose radiation exposure effects are seen as stochastic. At diagnostic levels, where doses are low, stochastic effects are random and the odds of having any effect are extremely low. A few people may experience an effect from the radiation exposure, but this cannot be predicted. Radiation risks from diagnostic imaging are considered to be stochastic. Also, heredity effects and carcinogenesis are considered to be stochastic (5). Ionizing radiation at high doses causes certain specific effects. Therefore, at certain doses, certain predictable outcomes can be determined. These are called nonstochastic, or deterministic, effects. These effects are very predictable and range from blood and chromosome aberrations to radiation sickness to certain death, depending on the dose, dose rate, age, immune capacity of an individual, and type of radiation exposure. For g- and x-ray radiation, exposure measured in grays and sieverts (rads and rems) is equal; however, this is not true of neutron radiation or when the quality factor is greater than 1 for the conversion between rads and rems. Nonstochastic (deterministic) effects include hematologic syndrome (pancytopenia), erythema, gastrointestinal syndrome (radiation sickness), and central nervous system syndrome (Table 2). One concept used to gauge toxicity is that of the lethal dose to 50% of the population (LD50) exposed to the agent observed at a specific time. The LD50 at 30 d (LD50/30) for humans due to ionizing radiation exposure is approximately 2.5–4.5 Gy (250–450 rad). This estimate for humans varies between different sources and is primarily empiric. Therefore, concrete data are not available. In other organisms, the LD50/30 factor has been established through experiments (Table 3) (5). Within the cumulative dose, the annual dose limit for an individual prescribed by AERB is more stringent at 30 mSv, as against the ICRP limit of 50 mSv
- Because doctors are unlikely to know the amount of radiation a person has received, they usually predict outcome based on the person's symptoms. The cerebrovascular syndrome is fatal within hours to a few days. The gastrointestinal syndrome generally is fatal within 3 to 10 days, although some people survive for a few weeks. Many people who receive proper medical care survive the hematopoietic syndrome, depending on the radiation dose and their state of health. Those who do not survive typically die within 4 to 8 weeks after exposure
- 1945: (Japan) atomic bomb attack approximately 120,000 to 140,000 civilians and military personnel instantly. and thousands more have died over the years from radiation sickness and related cancers. In April 2010, the locality of Mayapuri was affected by a serious radiological accident.[1] An AECL Gammacell 220 research irradiator owned by Delhi University since 1968, but unused since 1985, was sold at auction to a scrap metal dealer in Mayapuri on February 26, 2010.[2][3][4] The orphan source arrived at a scrap yard in Mayapuri during March, where it was dismantled by workers unaware of the hazardous nature of the device. The cobalt-60 source was cut into eleven pieces. The smallest of the fragments was taken by Ajay Jain who kept it in his wallet, two fragments were moved to a nearby shop, while the remaining eight remained in the scrap yard. All of the sources were recovered by mid-April and transported to the Narora Atomic Power Station, where it was claimed that all radioactive material originally contained within the device was accounted for. The material remains in the custody of the Department of Atomic Energy[5][6][7][8] Eight people were hospitalised as a result of radiation exposure, where one later died.[9]
- A range of synthetic, semisynthetic and herbal compounds have been screened as radiation countermeasure agents and a number of promising radiation countermeasure agents are under development
- KI (potassium iodide) is a salt of stable (not radioactive) iodine that can help block radioactive iodine from being absorbed by the thyroid gland, thus protecting this gland from radiation injury. The thyroid gland is the part of the body that is most sensitive to radioactive iodine. People should take KI (potassium iodide) only on the advice of public health or emergency management officials. There are health risks associated with taking KI. KI (potassium iodide) does not keep radioactive iodine from entering the body and cannot reverse the health effects caused by radioactive iodine once the thyroid is damaged. KI (potassium iodide) only protects the thyroid, not other parts of the body, from radioactive iodine. KI (potassium iodide) cannot protect the body from radioactive elements other than radioactive iodine—if radioactive iodine is not present, taking KI is not protective and could cause harm. Table salt and foods rich in iodine do not contain enough iodine to block radioactive iodine from getting into your thyroid gland. Do not use table salt or food as a substitute for KI. Do not use dietary supplements that contain iodine in the place of KI (potassium iodide). They can be harmful and non-efficacious. Only use products that have been approved by the U.S. Food and Drug Administration (FDA). Back to Top How does KI (potassium iodide) work? The thyroid gland cannot tell the difference between stable and radioactive iodine. It will absorb both. KI (potassium iodide) blocks radioactive iodine from entering the thyroid. When a person takes KI, the stable iodine in the medicine gets absorbed by the thyroid. Because KI contains so much stable iodine, the thyroid gland becomes “full” and cannot absorb any more iodine—either stable or radioactive—for the next 24 hours. KI (potassium iodide) may not give a person 100% protection against radioactive iodine. Protection will increase depending on three factors. Time after contamination: The sooner a person takes KI, the more time the thyroid will have to “fill up” with stable iodine. Absorption: The amount of stable iodine that gets to the thyroid depends on how fast KI is absorbed into the blood. Dose of radioactive iodine: Minimizing the total amount of radioactive iodine a person is exposed to will lower the amount of harmful radioactive iodine the thyroid can absorb. Back to Top Who can take KI (potassium iodide)? The thyroid glands of a fetus and of an infant are most at risk of injury from radioactive iodine. Young children and people with low amounts of iodine in their thyroid are also at risk of thyroid injury. Infants (including breast-fed infants) Infants have the highest risk of getting thyroid cancer after being exposed to radioactive iodine. All infants, including breast-fed infants need to be given the dosage of KI (potassium iodide) recommended for infants. Infants (particularly newborns) should receive a single dose of KI. More than a single dose may lead to later problems with normal development. Other protective measures should be used. In cases where more than one dose is necessary, medical follow up may be necessary. Children The U.S. Food and Drug Administration (FDA) recommends that all children internally contaminated with (or likely to be internally contaminated with) radioactive iodine take KI (potassium iodide), unless they have known allergies to iodine (contraindications). Young Adults The FDA recommends that young adults (between the ages of 18 and 40 years) internally contaminated with (or likely to be internally contaminated with) radioactive iodine take the recommended dose of KI (potassium iodide). Young adults are less sensitive to the effects of radioactive iodine than are children. Pregnant Women Because all forms of iodine cross the placenta, pregnant women should take KI (potassium iodide) to protect the growing fetus. Pregnant women should take only one dose of KI following internal contamination with (or likely internal contamination with) radioactive iodine. Breastfeeding Women Women who are breastfeeding should take only one dose of KI (potassium iodide) if they have been internally contaminated with (or are likely to be internally contaminated with) radioactive iodine. They should be prioritized to receive other protective action measures. Adults Adults older than 40 years should not take KI (potassium iodide) unless public health or emergency management officials say that contamination with a very large dose of radioactive iodine is expected. Adults older than 40 years have the lowest chance of developing thyroid cancer or thyroid injury after contamination with radioactive iodine. Adults older than 40 are more likely to have allergic reactions to or adverse effects from KI. Back to Top How is KI (potassium iodide) given? The FDA has approved two different forms of KI (potassium iodide), tablets and liquid, that people can take by mouth after a radiation emergency involving radioactive iodine. Tablets come in two strengths, 130 milligram (mg) and 65 mg. The tablets have lines on them so that they may be cut into smaller pieces for lower doses. For the oral liquid solution, each milliliter (mL) contains 65 mg of KI (potassium iodide). According to the FDA, the following doses are appropriate to take after internal contamination with (or likely internal contamination with) radioactive iodine: Newborns from birth to 1 month of age should be given 16 mg (¼ of a 65 mg tablet or ¼ mL of solution). This dose is for both nursing and non-nursing newborn infants. Infants and children between 1 month and 3 years of age should take 32 mg (½ of a 65 mg tablet OR ½ mL of solution). This dose is for both nursing and non-nursing infants and children. Children between 3 and 18 years of age should take 65 mg (one 65 mg tablet OR 1 mL of solution). Children who are adult size (greater than or equal to 150 pounds) should take the full adult dose, regardless of their age. Adults should take 130 mg (one 130 mg tablet OR two 65 mg tablets OR two mL of solution). Women who are breastfeeding should take the adult dose of 130 mg. Back to Top How often should KI (potassium iodide) be taken? Taking a stronger dose of KI (potassium iodide), or taking KI more often than recommended, does not offer more protection and can cause severe illness or death. A single dose of KI (potassium iodide) protects the thyroid gland for 24 hours. A one-time dose at recommended levels is usually all that is needed to protect the thyroid gland. In some cases, people can be exposed to radioactive iodine for more than 24 hours. If that happens, public health or emergency management officials may tell you to take one dose of KI (potassium iodide) every 24 hours for a few days. Avoid repeat dosing with KI (potassium iodide) for pregnant and breastfeeding women and newborn infants. Back to Top What are the side effects of KI (potassium iodide)? Side effects of KI (potassium iodide) may include stomach or gastro-intestinal upset, allergic reactions, rashes, and inflammation of the salivary glands. When taken as recommended, KI (potassium iodide) can cause rare adverse health effects related to the thyroid gland. These rare adverse effects are more likely if a person: Takes a higher than recommended dose of KI Takes the drug for several days Has a pre-existing thyroid disease. Newborn infants (less than 1 month old) who receive more than one dose of KI (potassium iodide) are at risk for developing a condition known as hypothyroidism (thyroid hormone levels that are too low). If not treated, hypothyroidism can cause brain damage. Infants who receive more than a single dose of KI should have their thyroid hormone levels checked and monitored by a doctor. Avoid repeat dosing of KI to newborns. Back to Top Where can I get KI (potassium iodide)? KI (potassium iodide) is available without a prescription. The Food and Drug Administration (FDA) External Web Site Icon has approved some brands of KI. People should only take KI (potassium iodide) on the advice of public health or emergency management officials. There are health risks associated with taking KI. More detailed information on KI (potassium iodide) can be found at the FDA Website.