04 carcinogenesis


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Carcinogenesis in Tumor Cell

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04 carcinogenesis

  1. 1. Ch 10 RadiationCarcinogenesis
  2. 2. A. Definition of late effects1. Late effects are due to damage of cells that survive but retain some legacy of the radiation exposure. a. germ cells → genetic mutation b. somatic cell → leukemia or cancer
  3. 3. B. Stochastic effects• Genetic effects and carcinogenesis• arise from the injury of a few cells, or a single cell, therefore has no dose threshold• All-or-none effect• The probability of the biological effect occuring increases with dose, however, the severity of the biological effect when it occurs does not.
  4. 4. C. Deterministic (Nonstochastic) effect• Somatic effect• caused by damage of an increasing # of cells and amounts of tissue.• severity increases with increasing dose• degenerative, e.g. cataracts, organ atrophy, and fibrosis• There is a threshold dose
  5. 5. D. Carcinogenesis: The Nature of the Problem Cancer induction is the most important somatic effect of low dose ionizing radiation. • Fig. 10-1, Fig. 10-2 • Quantitative data on cancer induction by rad. come from pop’ns irradiated for medical purposes and exposed to nuclear weapons. (high d/r, short exposure time)
  6. 6. Marie & Irene Curie(Both died of leukemia)
  7. 7. grafted skin skin cancerHands of a dentist who held X-ray film in patients’ mouth for 35 yrs(thumb was partially amputated)
  8. 8. Early human experience of radiation-induced cancer1. Skin cancer and Leukemia Early X-ray workers, physicists and engineers for accelerator2. Lung cancer Miners (radium)3. Bone cancer radium dial painters4. Hepatoma Thorotrast
  9. 9. E. The latent period• There is a delay before the initially transformed cell (cells) starts to divide and form a tumor. May be a further delay before the tumor assumes the malignant characteristics of growth and spread.• In general, three steps for cancer induction initiation → promotion → progression• Leukemia has the shortest latent period, a peak by 5-7 years, most occurs in the first 15 years.• Solid tumor have a longer latency, avg. 25 years (10-60 years).
  10. 10. F. Models for carcinogenesis1. Absolute risk model a. The risk from radiation is additional to the natural incidence, e.g. leukemia due to external beams; bone cancer due to ingestion of radionuclides. b. Absolute risk = cancer risk in irradiated pop’n - cancer risk in the unirrad control pop’n c. unit: # of cases of cancer/106 exposure persons/y/rem
  11. 11. 2. Relative risk model: Rad effect of cancer induction is to increase the natural incidence at all ages by a given factor.
  12. 12. Comittees Concerned with Risk Estamates1. Scholarly  United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR, established in 1955)  BEIR committee (National Academy of Sciences in the United States, setup in 1976)2. Comittees involved with radiation protection  ICRP (International Commission on Radiological Protection)  NCRP (National Council on Radiological Protection and Measurements)
  13. 13. Bone sarcoma in female dial painters
  14. 14. Relative risk (Straight line)
  15. 15. Estimated excess relative risk (ERR)
  16. 16. DDREF = 2
  17. 17. Secondary Malignancy in RT Patients% increase in relative risk for sarcomas in or nearthe treatment fields for patients who receivedradiotherapy relative to those who underwentsurgery for prostate cancers
  18. 18. G. Carcinogenesis in laboratoryanimals1. Fig. 10-11, incidence of myeloid leukemia in RF male mice.3. Characteristic of the curve- the incidence of malignancy increases with dose up to a maximum, usually 3-10 Gy, followed by a subsequent decrease with further increases in dose.
  19. 19. Incidence of radiation-induced leukemia in RF male mice
  20. 20. The low-dose data (≦ 2 Gy) came from A-Bombsurvivors; high-dose data refer to RT patients.
  21. 21. Excess Relative Riskfor LeukemiaExcess RelativeRisk for SolidCancer
  22. 22. Ch 11 HereditaryEffects of Radiation
  23. 23. Lethal ChromosomalDamage
  24. 24. Lethal ChromosomalDamage
  25. 25. Non-lethalchromosome damage
  26. 26. Non-lethal chromosomedamage
  27. 27. Translocation(normal) (will survive due to genome balance, but abnormal) Translocation(die due to (die due togenome genomeimbalance) imbalance)