Biological Effects of Ionizing Radiation Deterministic effects

Biological Effects of Ionizing Radiation Deterministic effects
Part No...., Module No....Lesson No. Part title IAEA Post Graduate Educational Course in Radiation Protection and Safety of Radiation Sources Biological Effects of Ionizing Radiation Deterministic effects Part III: Biological Effects of Ionizing Radiation Module III.2: Deterministic effects Lesson III.2.6: Effects of partial body irradiation Learning objectives: Upon completion of this lesson, the students will be able to: list threshold doses for deterministic effects in different organs explain radiation-induced damage of the skin, eye, lung, gonads, thyroid and skeleton. Activity: lecture Duration: 1 hour Materials and equipment needed: none References: UNSCEAR, Sources and Effects of Ionizing Radiation, 2000 Report to the General Assembly with Scientific Annexes, United Nations, New York (2000). IAEA - WHO. Diagnosis and treatment of radiation injuries, Safety Reports Series No. 2, IAEA, Vienna, 1998. Hopewell JW. The skin: It's structure and response to ionizing radiation. Int J Radiat Biol 1990; 57:751-73 IAEA REGIONAL BASIC PROFESSIONAL TRAINING COURSE ON RADIATION PROTECTION. September-October, Germany, Training materials. IAEA Training Course at IPSN. Medical Emergencies in Case of Radiological Accidents. November Training materials. Effects of partial body irradiation Lecture IAEA Post Graduate Educational Course Radiation Protection and Safe Use of Radiation Sources IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Part No...., Module No....Lesson No.
Part title Introduction Partial body irradiation may cause local radiation injury of the part of the body Sources of data for deterministic effects in man: side effects of radiotherapy effects on the early radiologists effects amongst survivors of the atomic bombs at Hiroshima and Nagasaki in Japan consequences of severe accidents Lecture notes: Data on deterministic effects in man has been collected from observations of the side effects of radiotherapy; from effects on the early radiologists; from the effects amongst survivors of the atomic bombs at Hiroshima and Nagasaki in Japan; and from the consequences of severe accidents, some in the nuclear industry and some involving radiographic sources. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Part title Content Threshold doses for deterministic effects in different organs Radiation-induced damage of the: Skin Eye Lung Gonads Thyroid Skeleton Lecture notes: The following topics are covered in the lesson: Threshold doses for deterministic effects in different organs Radiation-induced damage of the skin Radiation-induced damage of the eye Radiation-induced damage of the lung Radiation-induced damage of the gonads Radiation-induced damage of the thyroid Radiation-induced damage of the skeleton Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Part title Overview Partial body irradiation may cause local radiation injury of the part of the body Possible target: Skin Thyroid Lung Eye lens Gonads, etc Lecture notes: Those accidents in which small areas of the body are subjected to very high doses of ionizing radiation while the rest of the body is exposed only to relatively low doses, and therefore the clinical signs and symptoms featuring the acute radiation sickness (ARS) are usually missing, are referred as local radiation injuries. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Threshold of occurrence for local injury
Part No...., Module No....Lesson No. Part title Threshold of occurrence for local injury Organ or tissue Dose in less than 2 days, Gy Deterministic effects Type of effect Time of occurrence Skin 3 Erythema 1 – 3 weeks Thyroid 5 Hypothyroidism 1st – several years Lens of the eye 2 Cataract 6 months - several years Gonads Permanent sterility weeks Lung 8 Pneumonitis 1-3 months Lecture notes: The organs of the body have different sensitivities to radiation, therefore, dose thresholds for deterministic health effects are also different. The skin is especially sensitive to beta rays. A high local dose causes reddening of the skin after a few hours. Two weeks later hair of the skin falls off. Epilation of all hair is usually observed after a life threatening whole body dose of a few Sv. High local doses to the skin may damage and occlude the blood vessels of the skin, and ulcers and necrosis may develop. Such type of a damage can be very painful and invalidising, and amputation may be the only solution. Module 26 IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Part title Time of Onset of Clinical Signs of Skin Injury vs Dose Received Symptoms Dose range Time of onset (Gy) (day) Erythema Epilation > Dry desquamation Moist desquamation Blister formation Ulceration > Necrosis > >21 Lecture notes: Radiation injury of skin produces lesions similar to the thermal burns. In general, exposure to  radiation or low energy X-rays causes appearance of signs earlier than exposure to  radiation or high energy X-rays. Acute radiation effects in skin develop over a period of weeks (depending on localization and dose) and recover spontaneously. The peak reaction may be: Erythema Dry radiodermatitis Moist radiodermatitis Acute ulcerations may occur after very localized very high radiation doses in radiation accidents ( source in pocket). They are due to massive damage of the dermal and subcutaneous vascular connective tissue. Therefore they do not heal and require plastic surgery. Acute radiodermatitis is unpleasant and may be painful but is not dangerous unless it covers more than 25% of the body surface (as was the case from B rays from contaminated wet clothing in Chernobyl fire fighters). Acute radiodermatitis of>25% body surface was the major cause of acute death in the first night liquidators. Skin doses were >10Gy. Normally treatment is not required for acute radiodermatitis. Chronic radiation effects in skin are common in cured cancer radiotherapy patients. They are usually progressive over time. The normal clinically accepted late effect is moderate atrophy and some telangiectasia. The type of severe chronic radiation damage to skin depends on the depth dose distribution. IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Radiation injury of the skin: acute phase
Part No...., Module No....Lesson No. Part title Radiation injury of the skin: acute phase Inflammation: redness (erythema), swelling (oedema), elevated temperature Passive tissue compression: thrombosis, circulation disorders (insufficient blood supply) Tissue atrophy, necrosis: pain, acute ulceration moderate doses ( > 20 Gy): epidermal cell depletion (denudation) due to the mitotic death of the epidermal cells basal and viable upper layers with consecutive dry or moist desquamation, blistering of the epidermis and secondary dermal ulceration very high doses (>100 Gy surface dose): acute dermal necrosis within 2-3 weeks (interphase death of endothelial and fibroblast type cells; sometimes moist desquamation and blisters) Lecture notes: Normally radiation damage to the epidermis is related to the reproductive sterilisation of epidermal stem cells. The absence of cell production resulting in the appearance of epithelial denudation (moist desquamation), the time of appearance of which is linked to the total epidermal turnover time. This is approximately 30 days in man. Earlier epithelial denudation can only occur if basal and more specifically suprabasal cells are killed directly by high doses of radiation i.e. after exposures of 100 Gy from low energy, 0.3 MeV, -emitters. The full functional integrity of the skin will be preserved if there are sufficient surviving clonogenic cells within the basal layer, or within the shaft of hair follicles, to allow for rapid repopulation of the surface. Prolonged denudation of the epidermis after irradiation will result in dermal dehydration, infection and a secondary loss of the dermal layers (ulceration). Cell components of the dermis divide slowly and hence cell loss would normally be expressed over a period of months. The slow development of vascular insufficiency can, for specific radiation exposure conditions, result in ischemic dermal necrosis after a latent interval of 3-4 months. Lower doses may result in dermal thinning developing from approximately 3 months after irradiation. Atrophic skin is hard to the touch and has lost the flexibility/elasticity normally associated with skin. Necrosis of the dermis and even subcutaneous structures may also develop within a few weeks of irradiation after very high doses ( 100 Gy) to the dermis. These higher doses result in the direct killing of endothelial and fibroblasts within the dermis. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Radiation injury of the skin: late phase
Part No...., Module No....Lesson No. Part title Radiation injury of the skin: late phase Epidermal and dermal atrophy: (fragile skin) Insufficient blood supply Late necrosis with skin ulceration Occlusion of lymphatic vessels with local lymph stagnation: pain, late oedema Hyperkeratotic and fibrotic degeneration of the skin Decreased immunological defence of the skin with increased sensitivity against infections, etc Persistent or recurring pain Increased risk of skin malignancies Lecture notes: Late consequences of skin injury are the following: 1. Epidermal and dermal atrophy: (fragile skin) 1st phase: death of endothelial and fibroblast type cells 2nd phase: smooth muscle cell degeneration and hyalinisation of the small arterioles 2. Insufficient blood supply 3. Late necrosis with skin ulceration: (sometimes without apparent reason) 4. Occlusion of lymphatic vessels with local lymph stagnation: pain, late oedema 5. Hyperkeratotic and fibrotic degeneration of the skin: Epidermal hyperplasia: (hyperkeratosis) Dermal hyperplasia and hypertrophia (fibrosis, cheloid) 6. Decreased immunological defence of the skin with increased sensitivity against infections and other factors 7. Persistent or recurring pain 8. Increased risk of skin malignancies Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Radiation injury of the eye
Part No...., Module No....Lesson No. Part title Radiation injury of the eye Observations: X-ray treatment of eye tumors Radiation injuries: Lid erythema Conjunctivitis Cataract Retinopathy Lecture notes: The reports of acute effects of low-LET radiation on the human eye come mainly from x-ray treatment of eye tumors. Every tissue of the organ is susceptible to radiation injury, the effect of which is lessened when the dose is fractionated. Radiation-induced clinical syndromes of the lid and other ocular adnexa encompass a wide spectrum of disorders, ranging from transient lid erythema and mild conjunctivitis to comeal perforation and loss of the globe. Moreover radiation-induced changes of one surface structure may secondarily affect other external ocular surfaces. For example, damage to the lachrymal gland with resultant dry eye may lead to severe keratitis, comeal ulceratiori and perforation of the globe. The eyelids are the most sensitive adnex, responding to single doses of 2 Gy (hyperaemia). Partial epilation and keratitis may be seen after a single dose of 4-6 Gy. Higher doses may induce skin necrosis, decreased tear production (10 Gy) and lesions of the cornea and the iris (15-20 Gy). Lesions of the retina and the optic nerve have been described after fractionated radiotherapy, usually resulting in significant visual consequences when doses exceed Gy. These lesions are secondary to vascular damage. Cataract is a well-known radiation complication. A number of ocular lesions were observed at Chernobyl. The severity of these eye injuries was correlated with that of the acute radiation syndrome but could not be accurately related to the local dose, since beta-radiation accounted for a major part of the total. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Part title Cataract Cataract - any detectable change of the normally transparent lens of the eye Reason of development: Some abnormal metabolic disorder Chronic ocular infection Trauma Old age Ionizing radiation (radiation-induced cataract) Lecture notes: The word cataract is used to describe any detectable change of the normally transparent lens of the eye. The effect may vary from tiny flecks in the lens to almost complete opacification, resulting in total blindness. Cataracts are most usually associated with old age or less commonly with some abnormal metabolic disorder, chronic ocular infection, or trauma. It is also well known that sufficient exposure to ionizing radiations (such as x- or -rays, charged particles, or neutrons) may cause a cataract. Cell division continues throughout life, and so the lens may be regarded as a self-renewal tissue. It is, however, a most curious cellular system in that there appears to be no mechanism for cell removal. If dividing cells are injured by radiation. the resulting abnormal fibers are not removed from the lens but migrate toward the posterior pole; because they are not translucent, they constitute the beginning of a cataract. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Radiation-induced cataract
Part No...., Module No....Lesson No. Part title Radiation-induced cataract The threshold dose following a single exposure of low-LET radiation is 2 Gy, for neutrons 0.2 Gy Lowering the dose rate or extending the exposure period increases the ED50 value to an average of 9.3 Gy Estimated latency periods: 6 month to 35 years Doses of less than 0.1 Sv/year are not thought to present appreciable risk for detectable visual impairment Occupational exposure limit for the eye is 0.15 Sv (ICRP-60) Lecture notes: The cataractogenic potential of ionizing radiation was recognized as long ago as the beginning of the 20th century. Radiation cataractogenesis is the most common delayed radiation injury of deterministic nature, and is thought to result from damage to the anterior equatorial cells of the len’s epithelial tissue. These cells normally divide and migrate to the posterior portion of the lens, where they gradually lose their nuclei and become lens fibers. The lens tissue, like that of the testes and the brain, is separated from the rest of the body by a barrier system. As a result, it has no direct blood supply, no macrophages for phagocytosis, and no way to remove accumulated damage. As a result, damaged or dead lens cells increase their opacity during their migration, and radiation-induced cataract manifests itself in a form of a „dough-nut” shape opacity around the posterior equator. However, cataracts causing severe visual impairment are rather rare, even after relatively high doses. Small radiation doses may increase the opacity, but visually impairing cataract formation results from an accumulation of dead or injured cells, and therefore has a threshold. For low-LET radiation, this threshold is 2 Gy, high-LET neutrons have thresholds of less than 0.2 Gy (RBE of neutrons for their cataract inducing ability is about 10). Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Radiation-induced retinopathy
Part No...., Module No....Lesson No. Part title Radiation-induced retinopathy Threshold dose of retinal damage: Gy depending on: radiation quality, dose rate, fractionation, fraction size threshold for visual impairment: ~ 50 Gy occurrence: 35 Gy ~ 10%; 45 Gy ~ 66 %; 80 Gy ~ 100 % Latency period: 6 months to 3 years Clinical manifestation: microaneurysms of the capillaries “cotton-wool spots” intraretinal haemorrhages, and leakage of retinal vessels with exudates Lecture notes: Radiation retinopathy was first described by Stallard (1933) following radon seed implantation for treatment of retinoblastoma. Retinopathy after external beam and brachytherapy has been well documented in a large number of reports. Clinically it is characterized by microaneurysms of the capillaries, “cotton-wool spots”, intraretinal haemorrhages, and leakage of the retinal vessels with hard exudates. Progressive occlusion of small retinal vessels with secondary ischemia and edema can be observed subsequently. Chronic changes include vitreous haemorrhage, retinal detachment, retinal and optic nerve atrophy with blindness. Retinal vessels near the optic disk have special susceptibility for radiation damage. Fovea centralis, the most avascular part of the retina with a preponderance of small vessels, is probably the area most sensitive to vascular injury. Data about the threshold dose of retinal damage vary from Gy, depending on the therapeutic regime (radiation quality, dose rate, fractionation, fraction size). Ellsworth (1977) found that some vascular damage occurred in 10% of cases treated with 35 Gy, 66% with 45 Gy, and 100 % with 80 Gy. An increasing risk for visual impairment was observed if retinal doses exceeded 50 Gy. Addition of chemotherapy may potentiate radiation retinopathy by lowering the threshold dose or increasing the risk of developing blindness. Fraction size is considered the most important factor in producing retinal and optic nerve damage, and daily fractions are recommended to be less than 2 Gy. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Radiation-induced hypothyroidism
Part No...., Module No....Lesson No. Part title Radiation-induced hypothyroidism Threshold dose – 5 Gy of acute exposure within 2 days Latent period – years Pathophysiological mechanism involved: direct lesions to follicular cells alterations of vascular system immunological reactions Lecture notes: Direct irradiation of the thyroid gland may produce a broad spectrum of thyroid diseases. The most frequent consequence of thyroid irradiation is hypothyroidism. Other radio-induced thyroid diseases include autoimmune thyroiditis. Graves' disease, and euthyroid Graves' ophthalmopathy. The potentially long latent period between radiation exposure and the development of thyroid dysfunction means that patients who have received head or neck irradiation require periodic clinical and laboratory evaluation to avoid excess morbidity. The physiological events that lead to the wide variety of thyroid abnormalities observed after exposure of the thyroid to radiation are largely unknown. Direct lesions to follicular cells, alterations of vascular system, or immunologic reactions might be involved. The published incidence of hypothyroidism varies substantially as a result of differences in radiation techniques, doses and quality of follow-up evaluations. Total body irradiation for bone marrow transplantation has produced a 25 to 73% incidence of subclinical or overt hypothyroidism, with a lower incidence after fractionated rather than after single-dose regimens. Of the cases following fractionated irradiation, half occurred within 5 years, but hypothyroidism may develop more than 20 years after exposure. The influence of age is not well documented. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Deterministic radiation injury of the lung
Part No...., Module No....Lesson No. Part title Deterministic radiation injury of the lung Pheumonitis Threshold dose – 8 Gy of acute exposure Latent period – 1-3 months Fibrosis At the late stage and as a consequence of acute pneumonitis Latent period – 6 months Lecture notes: The effects of radiation injury to the lung have been extensively studied. After the thymus, the lung is the most radiosensitive organ in the thorax. Irradiation of the thorax induces pneumonitis at acute doses above 8 Gy. The increase in the dose between 8 and 12 Gy sharply augments the incidence of pneumonitis without affecting the time of onset, which is usually 1 to 3 months after exposure. This acute pneumonitis may lead to secondary fibrosis. From a clinical point of view, radiation-induced pulmonary reactions have been described as a three-phase process: latency (1 month), acute pneumonitis (several months), and fibrosis (from the 6th month). Pneumonitis and fibrosis have been attributed to different target cell populations. The early, latent phase is characterized by degenerative changes of type I and type n pneumocytes and of endothelial cells The intermediate phase of acute pneumonitisis characterized by a dose-dependent leakage of proteins in the alveolar space, thickening of alveolar septa, oedema of the interstitium, and changes to the capillaries in the number of type II pneumocytes and alveolar macrophages. The late phase of fibrosis is characterized by capillary loss, a further decrease in the number of type I pneumocytes and increased collagen deposition. Although the clinical phases described above are generally accepted, various authors propose different mechanisms: injury to the vascular network, damage to the epithelial cells, or an intricate combination of cause and effect have been suggested. Whatever mechanism is proposed, the standard description of radiation effects on the lungs does not explain the relation between the different phases. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Radiation-induced pulmonary reactions
Part No...., Module No....Lesson No. Part title Radiation-induced pulmonary reactions Phases of development: Latency degenerative changes of pneumocytes and of endothelial cells Acute pneumonitis dose-dependent leakage of proteins in the alveolar space thickening of alveolar septa oedema of the interstitium, and changes to the capillaries in the number of type II pneumocytes and alveolar macrophages Fibrosis capillary loss further decrease in the number of type I pneumocytes increased collagen deposition Lecture notes: From a clinical point of view, radiation-induced pulmonary reactions have been described as a three-phase process: latency (1 month), acute pneumonitis (several months), and fibrosis (from the 6th month). Pneumonitis and fibrosis have been attributed to different target cell populations. The early, latent phase is characterized by degenerative changes of pneumocytes and of endothelial cells. The intermediate phase of acute pneumonitisis characterized by a dose-dependent leakage of proteins in the alveolar space, thickening of alveolar septa, oedema of the interstitium, and changes to the capillaries in the number of type II pneumocytes and alveolar macrophages. The late phase of fibrosis is characterized by capillary loss, a further decrease in the number of type I pneumocytes and increased collagen deposition. Although the clinical phases described above are generally accepted, various authors propose different mechanisms: injury to the vascular network, damage to the epithelial cells, or an intricate combination of cause and effect have been suggested. Whatever mechanism is proposed, the standard description of radiation effects on the lungs does not explain the relation between the different phases. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Deterministic radiation injury of the gonads
Part No...., Module No....Lesson No. Part title Deterministic radiation injury of the gonads Sterility: Temporary Permanent Target organ: Testes Ovarium Lecture notes: Sterility could be the possible consequence of radiation exposure of the gonads. Depending on the dose of exposure, sterility could be temporary or permanent. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Deterministic radiation injury of the gonads (Cont’d)
Part No...., Module No....Lesson No. Part title Deterministic radiation injury of the gonads (Cont’d) Organ / consequence of exposure Threshold absorbed dose of exposure Acute, Sv Protracted, Sv/year Testes temporary sterility permanent sterility 0.15 3.0 0.4 2.0 Ovary 2.5 0.2 Lecture notes: Temporary sterility is induced by acute doses as low as 0.15 Gy in men. Permanent sterility is induced by doses above 3 Gy. In women, permanent sterility may be induced by acute doses above Gy. Older women are more susceptible, probably because of the age-related decrease in the number of follicules. In the testes, unlike in other tissues, fractionated doses are more harmful than acute exposures, because cells are progressing into sensitive stages. Spermatogonial cell necrosis can be detected in men at 4-6 hours after local irradiation, with cell kill completed by 12 hours. The more mature cells composing the second and third phases of spermatogenesis are unaffected by doses below 3 Gy. These cells maintain a normal sperm count during 45 days. The sperm count then begins to drop, approaching azoospermia 10 weeks after 1.0 Gy. Dose fractionation shortens the delay and lengthens the duration of the drop in the number of sperm cells. The probability of endocrine insufficiency is related to radiation dose, fractionation, and age. Doses that impair spermatogenesis and fertility trigger a pituitary feedback: follicle-stimulating hormone increases in blood and urine after doses to the testis higher than 0.1 Gy, and luteinizing hormone is elevated in blood after doses greater than 0.2 Gy. On the other hand, the testicular production of testosterone does not change significantly. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Deterministic radiation injury of the skeleton
Part No...., Module No....Lesson No. Part title Deterministic radiation injury of the skeleton Threshold dose – 5-10 Gy Children bones are more sensitive The severity of radiation-induced damage to growing bone depends on: the total radiation dose fractionation dose homogeneity volume irradiated symmetry of the volume irradiated patient's age, etc Lecture notes: The effect of radiation on epiphyseal bone growth is of great concern when children are exposed to radiation. Irradiation of long bone epiphysises may lead to leg length inequality. Partial exposure of a vertebral body may result in severe scoliosis. The epiphyseal plate is a complex structure composed of a number of specialized cell populations, several of which may be important targets for radiation damage. Although the relative importance of radiation effects on various compartments of the growth plate is not completely understood, it is obvious that rapidly dividing chondrocytes and endothelial growth buds are both highly sensitive to the effects of radiation. The severity of radiation-induced damage to growing bone is determined by a number of factors: the total radiation dose, fractionation, dose homogeneity, volume irradiated, symmetry of the volume irradiated, patient's age, etc. Evidence suggests that there is a continuous dose-effect relationship between 5 and Gy; it may be particularly steep between 15 and 30 Gy. The fractionation sensitivity of growing bone in humans is not really known. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Part title Summary This lecture presented materials about effects of partial body irradiation The following topics were covered in the lecture: threshold doses for deterministic effects in different organs, radiation-induced damage of the skin, eye, lung, gonads, thyroid and skeleton Comments are welcomed Let’s summarize the main subjects we did cover in this session. This lecture presented materials about effects of partial body irradiation. We did cover the topics describing threshold doses for deterministic effects in different organs, radiation-induced damage of the skin, eye, lung, gonads, thyroid and skeleton. Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Where to Get More Information
Part No...., Module No....Lesson No. Part title Where to Get More Information UNSCEAR, Sources and Effects of Ionizing Radiation, 2000 Report to the General Assembly with Scientific Annexes, United Nations, New York,2000 IAEA - WHO. Diagnosis and treatment of radiation injuries, Safety Reports Series No. 2, IAEA, Vienna, 1998 Hopewell JW. The skin: It's structure and response to ionizing radiation. Int J Radiat Biol 1990; 57:751-73 Add module code number and lesson title IAEA Post Graduate Educational Course in Radiation Protection and Safty of Radiation Sources

Biological Effects of Ionizing Radiation Deterministic effects

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