Membranes during dl-Ethionine Hepatocarcinogenesis Functional and Structural Alterations of Liver Ergastoplasmic

SUMMARY Different functional and structural properties of rat liver microsomes were studied during hepatocarcinogenesis induced by 0.25% m-ethionine. During the first to fourth months of ethionine feeding, great decreases of cytochrome P-450 content, reduced nicotinamide adenine dinucleotide phosphate-dependent lipid peroxidation, and aminopyrine demethylase activity occurred. No changes in the reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity were observed. These functional alterations were paralleled by an increase in membrane-free ribosomes and by changes in the relative proportions of phospholipid fatty acids in microsomes. After the end of ethionine feeding, when hyperplastic nodules and/or hepatomas were present, the above functional and structural parameters were studied in the latter tissues, as well as in surrounding nonnodular liver. Decreases in cytochrome P-450 content, lipid peroxidation, and aminopyrine demethylase activity were documented in hyperplastic nodules and hepatomas. In hepatomas, the alterations were more marked and decrease of reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity was also found. All these functional parameters were quite normal in surrounding nonnodular liver. Similarly, alterations in phospholipid fatty acid composition disappeared in surrounding nonnodular liver, but they partially persisted in both hyperplastic nodules and hepa-tomas. In contrast, the increase in membrane-free ribo-somes also occurred in surrounding nonnodular liver, although to a lower extent than in hyperplastic nodules and hepatomas. These data are discussed in relation to the problem of the cellular precursors of hepatomas.