1. RADIATION PROTECTION IN DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY L 3: Biological effects of ionizing radiation IAEA Training Material on Radiation Protection in Diagnostic and Interventional Radiology

5. Part 3: Biological effect of ionizing radiation Topic 1: Classification of radiation health effects IAEA Training Material on Radiation Protection in Diagnostic and Interventional Radiology

6. Radiation health effects DETERMINISTIC Somatic Clinically attributable in the exposed individual CELL DEATH STOCHASTIC somatic & hereditary epidemiologically attributable in large populations ANTENATAL somatic and hereditary expressed in the foetus, in the live born or descendants BOTH TYPE OF EFFECTS CELL TRANSFORMATION

12. DIRECT ACTION INDIRECT ACTION

16. Outcomes after cell exposure DAMAGE REPAIRED CELL DEATH (APOPTOSIS) TRANSFORMED CELL DAMAGE TO DNA

17. Outcomes after cell exposure DAMAGE REPAIRED CELL NECROSIS OR APOPTOSIS TRANSFORMED CELL DAMAGE TO DNA

18. How DNA is repaired ?

22. Outcomes after cell exposure DAMAGE REPAIRED CELL NECROSIS OR APOPTOSIS TRANSFORMED CELL DAMAGE TO DNA

23. Normal human lymphocyte: chromosomes uniformly distributed

24. Apoptotic cell: chromosomes and nucleus fragmented and collapsed into apoptotic bodies

25. Effects of cell death Acute dose (in mSv) Probability of cell death 5000 100%

26. Outcomes after cell exposure DAMAGE REPAIRED CELL NECROSIS OR APOPTOSIS TRANSFORMED CELL DAMAGE TO DNA

27. Chromosomal deletions

28. Chromosomal translocations

30. CANCER INITIATION TUMOR PROMOTION MALIGNANT PROGRESSION METASTASIS MALIGNANT TRANSFOMATION STEAM CELL DIVISION MUTATION NECROSIS OR APOPTOSIS

31. NORMAL TISSUE

32. CELL INITIATION An initiating event creates a mutation in one of the basal cells

33. DYSPLASIA More mutations occurred. The initiated cell has gained proliferative advantages. Rapidly dividing cells begin to accumulate within the epithelium.

34. BENIGN TUMOR More changes within the proliferative cell line lead to full tumor development.

35. MALIGNANT TUMOR The tumor breaks through the basal lamina. The cells are irregularly shaped and the cell line is immortal. They have an increased mobility and invasiveness.

36. METASTASIS Cancer cells break through the wall of a lymphatic vessel or blood capillary. They can now migrate throughout the body and potentially seed new tumors.

37. A simple generalized scheme for multistage oncogenesis Damage to chromosomal DNA of a normal target cell Failure to correct DNA repair Appearance of specific neoplasia-initiating mutation Promotional growth of pre-neoplasm Conversion to overtly malignant phenotype Malignant progression and tumour spread

38. 10 -6 10 -12 10 -9 10 -15 10 -3 1 second 1 hour 1 day 1 year 100 years 1 ms 10 0 10 9 10 6 10 3 Energy deposition Excitation/ionization Initial particle tracks Radical formation PHYSICAL INTERACTIONS PHYSICO-CHEMICAL INTERACTIONS BIOLOGICAL RESPONSE MEDICAL EFFECTS Diffusion, chemical reactions Initial DNA damage DNA breaks / base damage Repair processes Damage fixation Cell killing Promotion/completion Teratogenesis Cancer Hereditary defects Proliferation of "damaged" cells Mutations/transformations/aberrations T I M E ( s e c ) Timing of events leading to radiation effects.

39. Part 3: Biological effect of ionizing radiation Topic 2: Factors affecting the radiosensitivity IAEA Training Material on Radiation Protection in Diagnostic and Interventional Radiology

41. Radiosensitivity (2) Muscle Bones Nervous system Skin Mesoderm organs (liver, heart, lungs…) Bone Marrow Spleen Thymus Lymphatic nodes Gonads Eye lens Lymphocytes ( exception to the RS laws) Low RS Medium RS High RS

43. Part 3: Biological effect of ionizing radiation Topic 3: Dose-effect response curve IAEA Training Material on Radiation Protection in Diagnostic and Interventional Radiology

46. Skin reactions Injury Threshold Dose to Skin (Sv) Weeks to Onset Early transient erythema 2 <<1 Temporary epilation 3 3 Main erythema 6 1.5 Permanent epilation 7 3 Dry desquamation 10 4 Invasive fibrosis 10 Dermal atrophy 11 >14 Telangiectasis 12 >52 Moist desquamation 15 4 Late erythema 15 6-10 Dermal necrosis 18 >10 Secondary ulceration 20 >6 Skin damage from prolonged fluoroscopic exposure

47. Skin injuries

48. Skin injuries

50. Eye injuries

51. Part 3: Biological effect of ionizing radiation Topic 4: Whole body response: acute radiation syndrome IAEA Training Material on Radiation Protection in Diagnostic and Interventional Radiology

54. Part 3: Biological effect of ionizing radiation Topic 5: Effects of antenatal exposure and delayed effect IAEA Training Material on Radiation Protection in Diagnostic and Interventional Radiology

59. Part 3: Biological effects of ionizing radiation Topic 6: Epidemiology IAEA Training Material on Radiation Protection in Diagnostic and Interventional Radiology

65. Detectability limits in Radioepidemiology Number of people in study and control groups E F F E C T I V E D O S E ( m S v ) 5 10 -1 10 0 10 0 10 1 10 1 10 2 10 2 10 4 10 4 10 3 10 3 10 6 10 7 10 8 10 9 10 10 10 11 10 CHERNOBYL DOSES REGION OF DETECTABILITY REGION OF UNDETECTABILITY Theoretical limit of detectability due to statistical causes (90% confidence interval)

66. High and Low Spontaneous Cancer Rates Incidence/105 Tissue High Low Male / Female Male /Female Nasopharynx 2 3.3 9.5 0. 2 0. 1 Esophagus 2 0.1 8. 3 0.5 0. 2 Stomach 9 5.5 4 0.1 5. 2 2. 2 Colon 35.0 29.6 1.8 1.3 Liver 46.7 11.5 0. 7 0. 3 Lung+Bronchus 11 0.8 29.6 10.3 2 .4 Skin melanoma 33.1 29.8 0.2 0.2 Breast female 10 3 . 7 1 4 .6 Cervix 53.5 3.0 from UNSCEAR 2000

67. Data on irradiated populations Population Approximate Size Atomic bomb survivors Japan : 86 000 Atomic tests : Semipalatinsk/Altai 3 0 000 Marshallese islanders 2 8 00 Nuclear accidents : intervention teams Chernobyl (total) > 200 000 population Chernobyl (>185 kBq /m 2 137 Cs) 1 500 000 population Chelyabinsk (total) 70 000 Medical procedures : low LET iodine treatment and therapy ~ 70 000 chest fluoroscopy 64 000 children hemangioma treatment 14 000 high LET thorotrast angiography 4 2 00 Ra-224 treatment 2 8 00 Prenatal exposure (fetal radiography, atomic bombs) 6 000 Occupational exposure : workers nuclear industry (Japan, UK) 115 000 uranium miners 21 000 radium dial painters 2 5 00 radiologists 10 000 Natural exposure (Chinese, EC and US studies) several 100 000

70. Excess Solid-Tumor Deaths among Atomic-Bomb Survivors

71. Relative Mortality Risks at Different Times After Exposure 0.5 5 1950- 1954 1963- 1966 1959- 1962 1955- 1958 1971- 1974 1967- 1970 1975- 1978 1979- 1982 1 10 20 2 Interval of follow-up Atomic bomb survivors Estimated relative risk at 1 Gy All cancers except leukaemia (+ 4.8%/y) Leukaemia ( ~10.7%/y)

72. Relative Risks of Radon from Indoor Exposure and from Mining           0 100 200 300 400 500 0.3 1 0.5 0.6 2 0.4 Radon concentration Bq/m 3 Relative risk miner studies (cohorts) indoor studies (case controls) log-linear fit to indoor studies estimated from correlation study in different regions 1.5

73. Breast Cancer in Women Exposed to Fluoroscopy Observed/expected breast cancers      0 1 2 3 4 0 1 2 3 4 Mean absorbed dose (Gy)

74. Thyroid Tumors in Irradiated Children         0 0.05 0.1 0.15 0.2 0.25 0 2 4 6 8 10 Mean dose (Gy) Relative risk Thyroid Cancer Thyroid benign tumors

75. Thyroid Cancer Cases in Children after the Chernobyl Accident                                       86 87 88 89 90 91 92 93 94 95 96 97 98 0 20 40 60 80 100 Ukraine Russian Fed. Belarus No of Cases Children under 15 years of age at diagnosis

76. Thyroid Cancer in Children in the Chernobyl Region Region No of Cases before the accident after the accident Belarus (1977-1985) 7 (1986-1994) 390 Ukraine (1981-1985) 24 (1986-1995) 220 Russia ( Bryansk and Kaluga region only ) (1986-1995) 62 The data represent incidences (not mortality) and are preliminary results. Most excess cancers occurred since 1993. Thyroid cancer has a high rate of cure >90%, but many of the cancers found are of the aggressive papillary type.

77. Risk Estimates from Occupational Exposure Study Excess relative risk per Sv All cancer Leukemia UK National Registry Radiation Workers 0.47 (-0.12-1.20) 4.3 (0.4-13.6) 1,218,000 person years 34 mSv average dose US Workers -1.0 (<0-0.83 <0 (<0-3.4) 705,000 person years 32 mSv average dose Atomic Bomb Survivors 0.33 (0.11-0.6) 6.2 (2.7-13.8) 2,185,000 person years 251 mSv average dose

78. Doses and Risks for in Utero Radiodiagnostics Exposure Mean foetal dose Hered. Disease Fatal cancer (mGy) to age 14 y X Ray Abdomen 2.6 6.2 10 -5 7.7 10 -5 Barium enema 16 3.9 10 -4 4.8 10 -4 Barium meal 2.8 6.7 10 -5 8.4 10 -5 IV urography 3.2 7.7 10 -5 9.6 10 -5 Lumbar spine 3.2 7.6 10- 5 9.5 10 -5 Pelvis 1.7 4.0 10 -5 5.1 10 -5 Computed tomography Abdomen 8.0 1.9 10 -4 2.4 10 -4 Lumbar spine 2.4 5.7 10 -5 7.1 10 -5 Pelvis 25 6.1 10 -4 7.7 10 -4 Nuclear medicine Tc bone scan 3.3 7.9 10 -4 1.0 10 -4 Tc brain scan 4.3 1.0 10 -5 1.3 10 -4

79. Extrapolation by Additive and Multiplicative Risks Models Annual Probability of death /1000 persons Age Years 15 5 25 35 45 Following exposure to 2 Gy at an age of 45 years Spontaneous risks : increase with age : Radiation risks become apparent after a lag period (5) -10 years Additive risk models: imply constant risk independent of background. Multiplicative risk models: imply an increase proportional to background risk 55 60 65 70 75

80. Risk Probability Coefficients (ICRP) Tissue Probability of fatal Cancer (10 -2 /Sv) Population Workers Bladder 0.30 0.24 Bone marrow 0.50 0.40 Bone surface 0.05 0.04 Breast 0.20 0.16 Colon 0.85 0.68 Liver 0.15 0.12 Lung 0.85 0.68 Esophagus 0.30 0.24 Ovary 0.10 0.08 Skin 0.02 0.02 Stomach 1.10 0.88 Thyroid 0.08 0.06 Remainder 0.50 0.40 Total all cancers 5.00 4.00 Genetic effects weighted 1.00 0.50

81. Proportion of Fatal Cancers Attributable to Different Agents Agent or Class Percentage of all Cancer Disease Best estimate Range Smoking 31 29 - 33 Alcoholic beverages 5 3 - 7 Diet 35 20 - 60 Natural hormones 15 10 - 20 Infection 10 5 - 15 Occupation 3 2 - 6 Medicines, medical practices 1 0.5 - 2 Electromagnetic radiation 8 5 -10 Ionizing (85% from natural radiation*) 4.5 Ultraviolet 2.5 Lower frequency <1 Industrial products <1 <1 - 2 Pollution 2 <1 - 4 Other ? ?

84. Indicators of relative organ tissue risk 0.05 Remainder 0.01 Bone surface 0.01 Skin 0.05 Thyroid 0.05 Oesophagus 0.05 Liver 0.05 Breast 0.05 Bladder 0.12 Stomach 0.12 Lung 0.12 Colon 0.12 Bone marrow (red) 0.20 Gonads w T TISSUE OR ORGAN