A cellular dynamics model of experimental bladder cancer: analysis of the effect of sodium saccharin in the rat.

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.