Cell Growth Dynamics and DNA Alterations in Carcinogenesis

  • Samuel M. Cohen
  • Leon B. Ellwein


A biological model of carcinogenesis has been developed based on a two event process. The frequency of each event is dependent on the number of target cells, the frequency of their cell division, and the probability of a critical genomic error occurring with each cell division. A chemical can increase the likelihood of cancer by affecting either the rate of genomic errors (genotoxicity) or the rate of cell division, or both. Using these parameters a more rationale approach to quantitative risk assessment is proposed. Three chemicals are presented as examples of how genotoxic effects (2-acetylaminofluorene in the mouse liver, the “megamouse,” ED01 study) and proliferative effects (sodium saccharin) influence carcinogenesis and how genotoxic and proliferation effects can interact (2-acetylaminof luorene in the mouse bladder and N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide in the rat bladder). The influence of pharmacokinetics, metabolism, physiology, and cell kinetics on the carcinogenicity of specific compounds is illustrated, demonstrating the importance of mechanistic information in assessing potential risk.


Urinary Bladder Bladder Tumor Genotoxic Effect Increase Cell Proliferation Cancer Risk Assessment 
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© Birkhäuser Boston 1990

Authors and Affiliations

  • Samuel M. Cohen
  • Leon B. Ellwein

There are no affiliations available

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