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A Biological Basis for the Linear Non-Threshold Dose-Response Relationship for Low-Level Carcinogen Exposure

  • Roy E. Albert
Part of the Environmental Science Research book series (ESRH, volume 21)

Abstract

There is no escaping the need to quantitatively assess the risks from low-level carcinogen exposure in order to judge how much regulatory effort is appropriate to reduce cancer hazards to acceptable levels. However, it is clearly recognized that the levels of exposure and the associated cancer risks from contamination of the environment by carcinogens are almost invariably far below the level which are directly measurable either by animal experiments or epidemiological studies in exposed human populations. We are therefore forced to use mathematical extrapolation models to define the relationship between dose and effect at levels which can never be ascertained directly. There are a number of mathematical extrapolation models which fit dose-response data for tumor induction and yet which predict risks differing by order of magnitude at very low levels of exposure.1 None of these models has a sound basis in biological fact since we do not understand the pathogenesis of neoplasia at the cellular level. Perhaps the most plausible is the linear non-threshold dose-response model which was first adopted for use in the assessment of cancer risks from ionizing radiation2 and then more recently from chemical carcinogens.3 Its plausibility rests largely on the association between tumorigenicity and mutagenicity as common manifestations of genotoxicity and the linearity at low dose levels of the dose-response relationships for mutagenicity by ionizing radiation4 and chemicals.5

Keywords

Phorbol Myristate Acetate Phorbol Ester Mouse Skin Phorbol Myristate Acetate Carcinogen Exposure 
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.

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References

  1. 1.
    Panel on Carcinogenesis, Report on Cancer Testing in the Safety Evaluation of Food Additives and Pesticides, Toxicol. Appl. Pharmacol. 20:419–438 (1971).CrossRefGoogle Scholar
  2. 2.
    National Research Council, Advisory Committee on the Biological Effects of Ionizing Radiations, “The Effects on Populations of Exposure to Low Levels of Ionizing Radiation,” National Academy of Sciences, Washington, D.C. (1972).Google Scholar
  3. 3.
    R. E. Albert, R. E. Train, and E. Anderson, Rationale Developed by the Environmental Protection Agency for the Assessment of Carcinogenic Risks, J. Natl. Cancer Inst. 58(5):1537–1541 (1977).PubMedGoogle Scholar
  4. 4.
    National Research Council, Advisory Committee on the Biological Effects of Ionizing Radiations, “The Effects on Populations of Exposure to Low Levels of Ionizing Radiation,” National Academy of Sciences, Washington, D.C. (1980).Google Scholar
  5. 5.
    J. McCann and B. N. Ames. A Simple Method for Detecting Environmental Carcinogens as Mutagens, Ann. N. Y. Acad. Sci. 271:5–13 (1976).PubMedCrossRefGoogle Scholar
  6. 6.
    C. E. Land, J. D. Boice, Jr., R. E. Shore, J. E. Norman, and M. Tokunaga, Breast Cancer Risk from Low-dose Exposure to Ionizing Radiation: Results of Parallel Analysis of Three Exposed Populations of Women, J. Natl. Cancer Inst. 65:353–376 (1980).PubMedGoogle Scholar
  7. 7.
    G. W. Beebe, H. Kato, and C. E. Land, Studies of the Mortality of A-bomb Survivors. 6. Mortality and Radiation Dose, 1950–1974, Radiat. Res. 75:138–201 (1978).PubMedCrossRefGoogle Scholar
  8. 8.
    J. A. Staffa and M. A. Mehlman, eds., “Innovations in Cancer Risk Assessment (ED01 Study),” J. Environ. Pathol. Toxicol. 3(3):1–250 (1980).Google Scholar
  9. 9.
    B. L. Van Duuren, Tumor Promoting Agents in Two-Stage Carcinogenesis, Prog. Exp. Tumor Res. 11:31–68 (1967).Google Scholar
  10. 10.
    M. I. Diaz Gomez, P. F. Swann, and P. N. Magee, The Absorption and Metabolism in Rats of Small Oral Doses of Dimethylnitrosamine, Biochem. J. 164:497–500 (1977).Google Scholar
  11. 11.
    E. Scherer and P. Emmelot, Kinetics of Induction and Growth of Enzyme-deficient Islands Involved in Hepatocarcinogenesis, Cancer Res. 36:2544–2554 (1976).PubMedGoogle Scholar
  12. 12.
    H. Druckrey, Quantitative Aspects of Chemical Carcinogenesis, in: “Potential Carcinogenic Hazards from Drugs, Evaluation of Risks,” (VICC Monograph Series, Vol. 7) R. Truhart, ed., Springer-Verlag, New York (1967).Google Scholar
  13. 13.
    H. C. Pitot and A. E. Sirica, The Stages of Initiation and Promotion in Hepatocarcinogenesis, Biochim. Biophys. Acta 605:191–215 (1980).PubMedGoogle Scholar
  14. 14.
    T. J. Slaga, S. M. Fischer, L. Triplett, and S. Nesnow, Comparison of Complete Carcinogenesis and Tumor Initiation Promotion, a Reliable Short Term Assay, J. Environ. Pathol. Toxicol., in press.Google Scholar
  15. 15.
    R. K. Boutwell, Some Biological Aspects of Skin Carcinogenesis, Prog. Exp. Tumor Res. 4:207–250 (1964).PubMedGoogle Scholar
  16. 16.
    M. A. Pereira, F. J. Burns, and R. E. Albert, Dose Response for Benzo(a)pyrene Adducts in Mouse Epidermal DNA, Cancer Res. 39:2556–2559 (1979).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • Roy E. Albert
    • 1
  1. 1.Institute of Environmental MedicineNew York University Medical CenterNew YorkUSA

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