Models of hepatocarcinogenesis in the rat--contrasts and comparisons

A variety of approaches for the induction of altered hepatic foci, hyperplastic nodules, and hepatocellular carcinomas in rat liver have been developed. These protocols, aided by the appearance of preneoplastic lesions during the carcinogenic process, have proven to be very useful for examining many of the characteristics of events involved in rat hepatocarcinogenesis. A number of models have demonstrated distinct steps or stages in the progression of the carcinogenic process. These protocols are currently employed in the classification and distinction of agents effecting hepatocarcinogenesis at one or more of its stages. This review presents an overview of the present-day multistage hepatocarcinogenesis model systems in the rat, with contrasts and comparisons of these systems. The potential uses of the model systems in the identification of complete carcinogens, initiating agents, and promoting agents devoid of initiating action are discussed.