Quantitative analysis of enzyme-altered foci in rat hepatocarcinogenesis experiments--I. Single agent regimen

Considerable recent attention has focused on the quantitative analysis of enzyme-altered foci in rodent hepatocarcinogenesis experiments. These foci are believed to represent clones of premalignant cells. A method is presented for the quantitative analysis of these foci that takes into account both the total number of focal transections observed in each liver cross-section and the size distribution of these transections. The method, which has a natural interpretation within the framework of a two-mutation model for carcinogenesis, yields estimates of rates of initiation and of growth rates of enzyme-altered foci as functions of dose of the agent under consideration. Definitions of initiation and promotion potencies are proposed. The method is illustrated by application to an experiment in which rats were administered N-nitrosomorpholine at various concentrations in their drinking water.