Nodules Generated in Four Different Models in the Rat A Common Biochemical Pattern in Preneoplastic Hepatocyte

Hepatocyte nodules, structures consistently seen in every model of liver carcinogenesis well before the first appearance of cancer, were examined with respect to some Phase I and Phase II components considered to be important in the metabolism of carcinogens and other xenobiotics. Phase I components are those related to the metabolism of xenobiotics and include microsomal cytochromes P-450 and mixed-function oxygenase activities. Phase II components are those related to the conju gation and detoxification reactions of xenobiotics and their me tabolites and include glutathione S-transferases and glutathione. Nodules were induced by the resistant hepatocyte, cholinedeficient, methionine-low diet, phénobarbital and orotic acid models of liver carcinogenesis. Also, nodules generated by the resistant hepatocyte model were examined after transplantation to the spleen of syngeneic animals. The hepatocyte nodules show a common biochemical pattern, consisting of decreased microsomal cytochromes P-450, cytochrome b5, and aminopyrine A/-demethylase activity and increased glutathione and yglutamyltransferase in whole homogenates and glutathione Stransferase activity in the cytosol. This similarity, appropriate to a resistance phenotype, adds additional support for the hypoth esis that hepatocyte nodules may be a common step in liver carcinogenesis in several different models.