Decreased expression of cytochrome P-452 in the resistance phenotype characteristic of putative preneoplastic hepatocyte nodules during hepatocarcinogenesis.

Hepatocyte nodules, a characteristic early step in the development of liver cancer in rats, has a distinctive resistance phenotype including a large decrease in total cytochromes P-450 and in two isozymes induced by phenobarbital and two by 3-methylcholanthrene. In this study, it has been observed that the nodules show a large decrease in an additional cytochrome P-450, cytochrome P-452, which is very active in the hydroxylation of lauric acid at C-11 and C-12. The decrease in activity of this microsomal cytochrome P-452 is of the same order of magnitude as the decreases in the other cytochrome P-450 components. These observations are consistent with the hypothesis that there is some more basic alteration in the synthesis or availability of heme and that the changes in the activities of the cytochromes P-450 are secondary.