Computer Simulation of Chemical Carcinogenesis

  • Rory B. Conolly
  • Richard H. Reitz
  • Harvey J. ClewellIII
  • Melvin E. Andersen

Abstract

The standard procedure for evaluating carcinogen risk is the rodent bioassay coupled with statistically-based risk extrapolation. Extrapolation serves to bridge the physiological differences between the experimental species and man and between the experimental exposure scenario and that occurring in the “real world”. Little of what is known, however, about carcinogen pharmacokinetics, biochemical mechanisms of action, and cancer biology in either the experimental species or in man is used in risk assessment because no paradigm has been available to guide the incorporation of this information. Moolgavkar and Venzon (1979), and Moolgavkar and Knudson (1981), have described a biologically structured model of carcinogenesis (M-V-K model) that provides quantitative insights into the relationship between cellular proliferation, mutation, and tumor development. This is not, however, (and was not intended to be) a fully integrated model of chemical carcinogenesis as it lacks a biologically-based description of carcinogen pharmacokinetics, nor does it explicitly define biochemical mechanisms linking target tissue dose with tumorigenesis.

Keywords

Glutathione Adduct Methylene Chloride Macromolecule Biphenyl 

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Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Rory B. Conolly
    • 1
  • Richard H. Reitz
    • 2
  • Harvey J. ClewellIII
    • 3
  • Melvin E. Andersen
    • 3
  1. 1.NSI Technology Services, Corp.DaytonUSA
  2. 2.Mammalian and Environmental ToxicologyDow Chemical CompanyMidlandUSA
  3. 3.Toxic Hazards DivisionHarry G. Armstrong Aerospace Medical Research LaboratoryWright-Patterson AFBUSA

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