Assessing the effects of metabolism of environmental agents on cancer tumor development by a two-stage model of carcinogenesis.

By combining the Michaelis-Menten kinetics of metabolism with the two-stage model of Moolgavkar and Knudson (1981) and the extended two-stage model of carcinogenesis proposed by Tan and Gastardo (1985), this paper proceeds to investigate the effects of metabolism of carcinogens on cancer tumor development. It is shown that the nonlinear kinetics of metabolism of carcinogens affect the dose-response relationship mainly through the mutation rates. If the initiator is affected by metabolism, then the metabolism of promoters has very little or negligible effects of the expected incidences and the number of tumors.