The effects of various chemicals on the development of hyperplastic liver nodules in hepatectomized rats treated with N-nitrosodiethylamine or N-2-fluorenylacetamide.

The effects of various hepatocarcinogenic, non-hepatocarcinogenic and non-carcinogenic chemicals on the induction of hyperplastic liver nodules by N-nitrosodiethylamine (DEN) or N-2-fluorenylacetamide (2-FAA) as an initiator were studied in male Fischer 344 rats. Rats were injected intraperitoneally with 200 mg of DEN/kg body weight or were fed on basal diet containing 200 ppm of 2-FAA for 2 weeks, and then given various test chemicals starting from week 3. They were also partially hepatectomized in week 3. All animals were killed at the end of week 8 and examined histologically. For quantitative analysis, hyperplastic nodules in the liver were measured with a color video image processor, VIP-21C. The effect of various chemicals in rats treated with DEN or with 2-FAA were compared. The production of hyperplastic liver nodules was greatest in rats treated with strong hepatocarcinogens, and less in rats treated with weak hepatocarcinogens. Very few hyperplastic nodules were produced after treatment with non-hepatocarcinogens or noncarcinogens. Hyperplastic nodules were formed in rats treated with phenobarbital, which is a hepatopromoter. Saccharin, which is a urinary bladder promoter, did not enhance the production of hyperplastic nodules in the liver. These results indicate that many hepatocarcinogens enhance liver carcinogenesis. The classification of chemicals as liver carcinogens is discussed on the basis of the results.