DNA Damage and Carcinogenesis

  • R. B. Setlow
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 40)


A number of independent lines of evidence, other than cell biology ones, support the somatic mutation theory of cancer. They indicate that damage to DNA can lead to cancer and hence one should be concerned about environmental agents that react with DNA. Nevertheless, there are arguments against this point of view (1) and, even if damage to DNA is the important element in cancer initiation, one should always keep in mind the possibilities that the switch from normal to cancer cells may arise from faulty transcription and hence translation (as seems to be the case in the death of UV-irradiated arrested human fibroblasts). Moreover, promotion steps subsequent to initiation may be of overriding importance at the initiation doses received at low exposure-rate levels.


Skin Cancer Excision Repair Ataxia Telangiectasia Xeroderma Pigmentosum Ataxia Telangiectasia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    H. Rubin, Is somatic mutation the major mechanism of malignant transformation?, J. Natl. Canc. Inst. USA 64: 995 (1980).Google Scholar
  2. 2.
    B. N. Ames, Identifying environmental chemicals causing mutations and cancer, Science 204.: 587 (1979).Google Scholar
  3. 3.
    E. Huberman, Mutagenesis and cell transformation of mammalian cells in culture by chemical carcinogens, J. Environ. Pathol. Toxicol. 2: 29 (1978).PubMedGoogle Scholar
  4. 4.
    C. A. Jones and E. Huberman, A sensitive hepatocyte-mediated assay for the metabolism of nitrosamines in mutagens for mammalian cells, Cancer Res. 40: 406 (1980).PubMedGoogle Scholar
  5. 5.
    J. C. Barrett, T. Tsutsui, and P. 0. P. Ts’o, Neoplastic transformation induced by a direct perturbation of DNA, Nature 274: 229 (1978).PubMedCrossRefGoogle Scholar
  6. 6.
    R. W. Hart, R. B. Setlow, and A. D. Woodhead, Evidence that pyrimidine dmers in DNA can give rise to tumors, Proc. Natl. Acad. Sci. USA 74: 5574 (1977).PubMedCrossRefGoogle Scholar
  7. 7.
    R. B. Setlow, Repair deficient human disorders and cancer, Nature 271: 713 (1978).PubMedCrossRefGoogle Scholar
  8. 8.
    C. F. Arlett and A. R. Lehmann, Human disorders showing increased sensitivity to the induction of genetic damage, Ann. Rev. Genet. 12: 95 (1978).PubMedCrossRefGoogle Scholar
  9. 9.
    E. C. Friedberg, U. K. Ehmann, and J. I. Williams, Human diseases associated with defective DNA repair, Adv. Radiat. Biol. 8: 85 (1979).Google Scholar
  10. 10.
    A. D. Andrews, S. F. Barret, and J. H. Robbins, Xeroderma pigmentosum abnormalities correlated with colony-forming ability after ultraviolet radiation, Proc. Natl. Acad. Sci. USA 75: 1984 (1978).Google Scholar
  11. 11.
    D. G. Harnden, Mechanisms of Genetic Susceptibility, in: “13th Jerusalem Symposium on Carcinogenesis: Fundamental Mechanisms and Environmental Effects,” D. Reidel, Dordrecht (1980).Google Scholar
  12. 12.
    B. Konze-Thomas, J. W. Levinson, V. M. Maher, and J. J. McCormick, Correlation among the rates of dimer excision, DNA repair replication, and recovery of human cells from potentially lethal damage induced by ultraviolet radiation, Biophys. J. 28: 315 (1979).PubMedCrossRefGoogle Scholar
  13. 13.
    V. M. Maher, D. J. Dorney, A. L. Mendrala, B. Konze-Thomas, and J. J. McCormick, DNA excision-repair processes in human cells can eliminate the cytotoxic and mutagenic consequences of ultraviolet irradiation, Mutat. Res. 62: 311 (1979).PubMedCrossRefGoogle Scholar
  14. 14.
    T. Kakunaga, Relationship between transformation and mutation in mammalian cells, in: “13th Jerusalem Symposium on Carcinogenesis: Fundamental Mechanisms and Environmental Effects,” D. Reidel, Dordrecht (1980).Google Scholar
  15. 15.
    J. Doniger and J. A. DiPaolo, Excision and postreplication repair capacities, enhanced transformation, and survival of Syrian hamster cells irradiated by ultraviolet light, Cancer Res. 40: 582 (1980).PubMedGoogle Scholar
  16. 16.
    R. Goth and M. F. Rajewsky, Persistence of 06-ethylguanine in rat brain DNA: Correlation with nervous system-specific carcinogenesis by ethylnitrosourea, Proc. Natl. Acad. Sci. USA 71: 639 (1974).PubMedCrossRefGoogle Scholar
  17. 17.
    R. Mueller and M. F. Rajewsky, Sensitive radioimmunoassay for detection of O6-ethyldeoxyguanosine in DNA exposed to the carcinogen ethylnitrosourea in vivo or in vitro, Zeit. f. Naturforsch. 33C: 897 (1978).Google Scholar
  18. 18.
    M. C. Poirier, M. A. Dubin, and S. H. Yuspa, Formation and removal of specific acetylaminofluorene-DNA adducts in mouse and human cells measured by radioimmunoassay, Cancer Res. 39: 1377 (1979).PubMedGoogle Scholar
  19. 19.
    M. C. Paterson, Use of purified Lesion-recognizing enzymes to monitor DNA repair in vivo, Adv. Radiat. Biol. 7: 1 (1978).Google Scholar
  20. 20.
    E. L. Scott and M. L. Straf, Ultraviolet radiation as a cause of cancer, in: “Origins of Human Cancer,” H. H. Hiatt, J. D. Watson, and J. A. Winston, eds., Cold Spring Harbor Laboratory, N. Y. (1977).Google Scholar
  21. 21.
    J. Scotto and T. Fears, quoted in: “Protection against depletion of stratosphere ozone by chlorofluorocarbons,” Natl. Acad. Sci., Washington (1979).Google Scholar
  22. 22.
    G. J. Kantor, J. C. Sutherland, and R. B. Setlow, Action spectra for killing non-dividing normal human and xeroderma pigmentosum cells, Photochem. Photobiol. 31: 459 (1980).CrossRefGoogle Scholar
  23. 23.
    R. D. Rundel and D. S. Nachtwey, Skin cancer and ultraviolet radiation, Photochem. Photobiol. 28: 345 (1978).PubMedCrossRefGoogle Scholar
  24. 24.
    J. E. Cleaver and D. Bootsma, Xeroderma pigmentosum: Biochemical and genetic characteristics, Ann. Rev. Genet. 9: 19 (1975).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • R. B. Setlow
    • 1
  1. 1.Biology DepartmentBrookhaven National LaboratoryUptonUSA

Personalised recommendations