The inhibitory effect of copper on DL-ethionine carcinogenesis in rats.

Summary This paper concerns the study of the inhibitory effect of cupric acetate (CU) on various hepatic changes in rats, including the development of hepatomas induced by dl-ethionine (ethionine). By the addition of 0.25% CU, hepatoma induction was prevented in rats fed diets containing 0.25% ethionine for 24 weeks. The inhibitory effect of CU depended on the administration period. The induction of hepatomas after 24 weeks by diets that contained ethionine was completely prevented by the addition of CU for 12, 16, or 20 weeks but not by its addition for only 4 or 8 weeks. CU did not inhibit the proliferation of nodular hyperplasia induced in rats by ethionine. Nodular hyperplasia was not seen in the liver of rats treated with ethionine and CU for 20 weeks, but it developed in the liver of rats treated with ethionine and CU for 4 to 16 weeks. Histochemical examination showed deposits of copper in the liver in parenchymal cells in periportal areas but not in Kupffer cells, oval cells, or cells of bile duct epithelium. Electron microscopy showed dense bodies surrounded by a single membrane in the liver parenchymal cells of rats treated with ethionine and CU but not in those of rats treated with ethionine alone. Biochemical examination showed that the copper content of the liver increased in rats treated either with ethionine plus CU or with CU alone. After treatment with ethionine and CU, the nuclear fraction had the highest copper concentration, followed by the supernatant fraction.