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

Considerable recent attention has focused on the quantitativeanalysis of enzyme-altered foci in rodent hepatocarcinogenesisexperiments. These foci are believed to represent clones premalignantcells. A method is presented for the quantitative analysis ofthese foci that takes into account both the total number offocal transections observed in each liver crosssection and thesize distribution of these transections. The method, which hasa natural interpretation within the framework of a two-mutationmodel for carcinogenesis, yields estimates of rates of initiationand of growth rates of enzyme-altered foci as functions of doseof the agent under consideration. Definitions of initiationand promotion potencies are proposed. The method is illustratedby application to an experiment in which rats were administeredN-nitroso morpholine at various concentrations in their drinkingwater.