Production of Both 8‐Hydroxydeoxyguanosine in Liver DNA and γ‐Glutamyltransferase‐positive Hepatocellular Lesions in Rats Given a Choline‐deficient, l‐Amino Acid‐defined Diet

Abstract

The comparative carcinogenic activities of a choline‐deficient, l‐amino acid‐defined diet (CDAADD) and a purified choline‐deficient diet (CDD) for rat liver were studied in terms of both 8‐hydroxy‐deoxyguanosine induction, a marker of DNA damage induced by oxidative stress, and development of γ‐glutamyltransferase(GGT)‐positive putative preneoplastic lesions, including foci and hyperplastic nodules. Twelve weeks after the beginning of treatment, DNA damage could be detected in the liver DNA of rats receiving either CDAADD or CDD, the degree being significantly greater in the former case. Similarly, while GGT‐positive liver lesions were induced by both CDAADD and CDD, the numbers were higher and the areas of lesions were larger in rats receiving CDAADD than in those given CDD. Histologically, hyperplastic nodules were induced in the livers of animals administered CDAADD whereas only foci were seen in the CDD case. The results thus indicate that oxidative stress might be directly involved in rat liver carcinogenesis by CDD and, to a greater degree, with CDAADD.