1. Introduction to Radiation Health: Late Effects - Cancer Dr. Niel Wald

2. Radiobiological Effects • Non-Stochastic • Severity varies with dose • May have threshold (cataract, dermatitis) • Stochastic • Probability of occurrence in population varies with dose • No threshold (cancer, genetic damage) 227-4

3. Intracellular Effects of Radiation 138-A

4. 395-4 Classification of Neoplasms

5. Basis for Tumor Dose:Response Estimates 175-3

6. Tumor Growth Curve 395-6

7. Scheme for Induction of Cancer by Environmental Carcinogens Normal Cells Initiator(s) (electrophilic, mutagenic) Chemical or Radiation Carcinogen Initiated Cells Tumor Cells Promoter(s) Clones Inactive Metabolites Gross Tumors 395-11 Courtesy of Miller and Miller

8. 395-1

9. 395-2

10. 395-3

11. Three germ layers and the tissues derived from them 666-1

12. Histogenetic classification of benign tumors 642-1

13. Histogenetic classification of malignant tumors 642-2(1)

14. Histogenetic Classification of Malignant Tumors with Atypical Nomenclature: 642-2(2)

15. Mechanisms of Cell Death 642-3

16. Cell Death (necrosis and apoptosis) 642-4

17. Maturation Arrest 642-6

18. Metastasis Formation 666-2

19. Metastasis Formation 666-3

20. Cancer Development 395-16

21. General Properties of Initiating Agents & Promoting Agents *defined in a broad sense as agents that can both initiate cancer in limited dosages and induce cancer in higher dosages or in states of increased host susceptibility 395-15

22. Properties of Oncogenes and Tumor Supressor Genes 666-9 * From Rudden, 1995b, with permission.

23. International Leukemia Incidence 666-4

24. Alternative Radiation Dose-Response Curves 227-5

25. Cancer Summary • Tissues vary considerably with respect to their sensitivity to cancer induction. • The major sites of solid tumors induced by whole-body exposure to radiation are the breast, thyroid, lung and digestive organs. • Age, both at the time of exposure and diagnosis, is a very important variable relating to cancer induction. • The latency period (time from exposure to tumor detection) is frequently very long, i.e. years to decades. • Interaction between host and environmental factors (i.e., hormonal influences, exposure to other carcinogenic agents) may play a significant role in tumor induction. • Nearly all the tissues in the body are susceptible to tumor induction. • The dose-response relationships for many animal model systems are qualitatively similar to those for human tumor induction. However, direct quantitative risk extrapolation from animals to man would be inappropriate 395-28

26. Radiation Cancer Risk Estimation 341-2

27. Radiation-induced Cancer Risk 227-6

28. Absolute Risk Model 220-4

29. Relative Risk Model 220-5

30. Dose-response Interpolation Curves 227-1

31. Radiation Dose:Slope Relationships 227-2

32. Radiation Dose Rate Ranges 227-3

33. Hiroshima Dose:Distance Relationship 92-I

34. ABCC Shielding History Floor Plan 93-C

35. A-Bomb Leukemia Cases by Year 100-C

36. A-Bomb Leukemia by Type and Dose 96-B

37. A-Bomb Leukemia Dose-Response Curves 302-5

38. A-Bomb Exposure Age vs.Leukemia Risk 220-2

39. The quadratic risk coefficient () has increased, whereas the linear low-dose risk coefficient () has decreased, suggesting that currently accepted standards for low-level gamma exposures are not in need of revision on the basis of changes in data from Japan. Risk Coefficients for Leukemia Mortality Risk Coefficient 10 rad (Cases/106/year/rad)100 rad Source: Adapted from Straume and Dobson (1981). Reproduced from Health Physics, Vol. 44 by permission of the Health Physics Society 303-4

40. The observed and expected numbers of Ankylosing Spondylitis deaths due to leukemia and aplastic anemia, 1935 - 54 study series Number of Deaths Significance of difference between observed and maximum expected number of deaths: Leukemia: P < 0.000001 Aplastic anemia: P < 0.000001 104-E

41. Spondylitis: Leukemia Dose-Response 104-G

42. Spondylitis: Leukemia Latency Postexposure 104-F

43. Incidence of Death from Leukemia in Physicians 104-D

44. Risk of Leukemia in various Diseases and Conditionsa,b a Risk of leukemia in various groups with specific epidemiologic and pathologic characteristics in populations followed for 10-30 years. b Leukemia risk (lifetime): Mortality increment from single exposure to 1 rad is 15-25 cases/106 persons or ~ 1/50,000. c Free in air doses (rads): gamma rays > 500 rads; neutrons > 60 rads Source: Modified from Miller (1970; from Brent (1980) 303-5

45. Leukemia Risk 96-I

46. A-Bomb: Mortality Relative Risks 173-1

47. A-Bomb: Cancer Relative Risks 173-2

48. A-Bomb: Cancer Dose-Response 173-3

49. 668-29

50. Thyroid Cancer Risk Associated with I-131 Exposure from Chernobyl Estimated Thyroid Dose from I-131 (Gy) Adapted from Astakhova et al., 1998 668-5