Dose relationships in experimental carcinogenesis: dependence on multiple factors including biotransformation.

The probability of obtaining a tumor in a carcinogenesis bioassay depends mainly on the time on test and on the dose of carcinogen used. There is very limited data on the shape of this surface or reliable data on dose-response or time on test-response relationships. Ullrich's data on tumor induction by low dose radiation shows a variety of shapes of curve depending on the tissue chosen for investigation. As radiation probably does not concern the processes involved in xenobiotic metabolism, these observations clearly demonstrate that factors other than metabolism are important. An attempt is made to discuss the shape of the dose-response curve in relation to a number of factors including the background incidence of tumors in a tissue, mechanisms of "nongenotoxic" or toxicity-related carcinogenesis, and xenobiotic activation of carcinogens.