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A Cellular Dynamics Model of Experimental Bladder Cancer: Analysis of the Effect of Sodium Saccharin in the Rat

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  • Leon B. Ellwein
  • Samuel M. Cohen

Abstract

To make the methodology of risk assessment more consistent with the realities of biological processes, a computer‐based model of the carcinogenic process may be used. A previously developed probabilistic model, which is based on a two‐stage theory of carcinogenesis, represents urinary bladder carcinogenesis at the cellular level with emphasis on quantification of cell dynamics: cell mitotic rates, cell loss and birth rates, and irreversible cellular transitions from normal to initiated to transformed states are explicitly accounted for. Analyses demonstrate the sensitivity of tumor incidence to the timing and magnitude of changes to these cellular variables. It is demonstrated that response in rats following administration of nongenotoxic compounds, such as sodium saccharin, can be explained entirely on the basis of cytotoxicity and consequent hyperplasia alone.

Suggested Citation

  • Leon B. Ellwein & Samuel M. Cohen, 1988. "A Cellular Dynamics Model of Experimental Bladder Cancer: Analysis of the Effect of Sodium Saccharin in the Rat," Risk Analysis, John Wiley & Sons, vol. 8(2), pages 215-221, June.
    • Handle: RePEc:wly:riskan:v:8:y:1988:i:2:p:215-221
    DOI: 10.1111/j.1539-6924.1988.tb01174.x
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    Cited by:

    1. Wilson, James D., 1996. "Thresholds for Carcinogens: A Review of the Relevant Science and Its Implications for Regulatory Policy," Discussion Papers 10470, Resources for the Future.
    2. Suresh H. Moolgavkar & Anup Dewanji & David J. Venzon, 1988. "A Stochastic Two‐Stage Model for Cancer Risk Assessment. I. The Hazard Function and the Probability of Tumor," Risk Analysis, John Wiley & Sons, vol. 8(3), pages 383-392, September.
    3. Duncan J. Murdoch & Daniel Krewski & John Wargo, 1992. "Cancer Risk Assessment with Intermittent Exposure," Risk Analysis, John Wiley & Sons, vol. 12(4), pages 569-577, December.

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