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Abstract

Following previous findings that feeding a choline-deficient (CD) diet to rats strongly promotes the evolution of liver cells, initiated by a chemical carcinogen, to foci of y-glutamyltranspeptidase (yGT)-positive hepatocytes, we investigated whether a CD diet could also promote the evolution of yGT-positive foci to hepatomas. yGT-positive foci were induced in male Sprague-Dawley rats by administration of a single dose of diethyInitrosamine 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 yGT-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 yGT-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 yGT-positive foci are reversible lesions.