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© 1990 Oxford University Press

other

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

Suresh H. Moolgavkar 3, E.Georg Luebeck 3, Mathisca de Gunst 1, Ruediger E. Port 2 and Michael Schwarz 2

3Division of Public Health Sciences, Fred Hutchinson Cancer Research Center 1124 Columbia Street, Seattle, WA 98104, USA
1Department of Mathematics, Free University De Boelelaan 1081, 1081 HV Amsterdam, The Netherlands
2Institute of Biochemistiy, German Cancer Research Center Im Neuenheirmer Feld 280, 6900 Heidelberg, FRG

Considerable recent attention has focused on the quantitative analysis of enzyme-altered foci in rodent hepatocarcinogenesis experiments. These foci are believed to represent clones 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 crosssection 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-nitroso morpholine at various concentrations in their drinking water.


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