Phosphatidylcholine peroxidation and liver cancer in mice fed a choline-deficient diet with ethionine

Abstract

A high incidence of hepatocellular carcinoma (HCC) was observed in mice fed a choline-deficient diet containing 0.1% ethionine (CDE) for 19 months. HCC was present in 85% of CDE mice and in 22% of choline-deficient (CD) mice not receiving ethionine. This strong hepatocarcinogenicity of the CDE diet was concomitant with a severe decrease in plasma and liver α-tocopherol (Toc) to 60 and 35%, respectively, of those contained in choline-supplemented (CS) control mice. We previously found that this dietary-induced HCC was preceded at 4-week feeding by a depletion of Toc and a remarkable increase of phosphatidylcholine hydroperoxide (PCOOH) in the livers of CDE mice. When HCC was prominent in CDE mice, PCOOH was still elevated. Mouse glutathione S-transferase (GST) M II isozyme, which is related to rat GST-P form, a positive marker for rat hepatic preneoplastic and neoplastic lesions, revealed an inverse histochemical pattern as that seen in rats (i.e., the HCC lesions tended to decreased staining). The aforementioned results taken together indicate that decreases in Toc and enhanced PC peroxidation are important events in CDE-induced mice liver tumors.