Hepatocarcinogenesis by diethylnitrosamine in rats fed high dietary levels of lipotropes.

The effects of high dietary levels of lipotropes on the carcinogenic activity of diethylnitrosamine (DENA) in rats were studied. All animals given DENA, with or without a dietary supplement, developed hepatocellular carcinomas. The mean survival times of all groups of rats dying with hepatocellular carcinomas after DENA treatment were determined. Choline, betaine, and folic acid consistently exerted no significant effect on those mean survival times. In rats receiving approximately equal to 2 mg DENA/day, methionine administration led to a slight but significant increase in the mean survival time of the carcinogen-treated rats, whereas vitamin B12 significantly lowered the survival time; neither substance altered the mean survival times of those treated with only 1.0 mg DENA/day. On the other hand, ethanolamine decreased the mean survival times of rats given 1.0 mg DENA daily, but had no effect on animals receiving 2 ml/day of carcinogen. Dimethylthetin (sulfur analogue of betaine), methotrexate, lecithin, and cephalin exerted no effect on the carcinogenic activity of DENA. The administration of dimethylthetin and betaine along with DENA led to markedly increased liver weights in animals dying of hepatocellular carcinomas, when compared to liver weights of animals treated with DENA alone.