Hepatocarcinogenic and promoting action of a choline-devoid diet in the rat.

Male Fisher 344 rats were solely fed a choline-supplemented diet for 65 to 105 weeks or a choline-devoid diet for 24 to 102 weeks. Hepatocellular carcinomas developed in the latter animals, beginning at 24 weeks. Other groups of rats were given a single dose of 20 mg diethylnitrosamine/kg, 18 h after a partial hepatectomy and were fed, 4 weeks thereafter, either a choline-supplemented, or a choline-devoid diet for up to 48 weeks. In rats fed the choline-supplemented diet, the only relevant lesion observed was a small transect number of foci of enzyme-altered hepatocytes. On the other hand, a significant number of foci, of preneoplastic nodules, and of hepatocellular tumors developed in rats fed the choline-devoid diet. The results obtained are consistent with those previously reported by others, indicating that diets devoid of choline, or of choline and methionine, are carcinogenic. The diets appear to act as complete carcinogens, since they are also efficient promoters of chemical hepatocarcinogenesis, as shown again, in the present study, by the results obtained in the diethylnitrosamine-pretreated rats.