Progression of carcinogen-induced foci of gamma-glutamyltranspeptidase-positive hepatocytes to hepatomas in rats fed a choline-deficient diet

Abstract

Following previous findings that feeding a choline-deficient (CD) diet to rat strongly promotes the evolution of liver cells, initiated by a chemical carcinogen, to foci of gamma-glutamyltranspeptidase (gamma GT)-positive hepatocytes, we investigated whether a CD diet could also promote the evolution of gamma GT-positive foci to hepatomas. gamma GT-positive foci were induced in male Sprague-Dawley rats by administration of a single dose of diethylnitrosamine followed by 2 weeks' feeding on a CD diet containing 0.02% acetylaminofluorene. Immediately thereafter, one group of rats was fed a plain CD diet and the other a choline-supplemented (CS) diet, and subgroups of animals were killed periodically for analysis of the number and size of gamma GT-positive foci and development of hepatomas. During the first 7 weeks after switching the diets, the number and size of the foci increased in both groups. At 12 and 16 weeks, the number and size of foci began to decline in rats fed the CS diet. However, in the CD group, there was a progressive increase in the size with coalescence of the foci, as well as development of neoplastic nodules. These lesions were followed at 20 and 28 weeks by development of hepatomas at a high incidence rate. In rats fed the CS diet, a few scattered gamma GT-positive foci, and small neoplastic nodules remained in the liver at 20 and 28 weeks, but no hepatomas developed. These results show that the CD diet is a potent promoter of the evolution of foci of altered hepatocytes to hepatomas, and that most of the gamma GT-positive foci are reversible lesions.