Induction of hyperplastic liver nodules in Wistar and MRC-Wistar rats by phenobarbital and the liver carcinogens acetoxime, 1-nitroso-5,6-dihydrouracil and 3-nitroso-2-oxazolidinone

We tested the ability of phenobarbital and two liver carcinogens, acetoxime and 1-nitroso-5,6-dihydrouracil (NDHU), to induce hyperplastic liver nodules (HLN) in MRC-Wistar and Wistar rats, using a system that included a single diethylnitrosamine (DEN) treatment, partial hepatectomy, and administration of the test compound in drinking water for 8 weeks. All three compounds induced significant HLN frequencies (number of HLN/cm2) in both rat strains. When the results for each strain were "normalized" for each compound and then combined, HLN frequency in MRC-Wistar rats was significantly lower (P less than 0.01) than that in Wistar rats. The weak liver carcinogen 3-nitroso-2-oxazolidinone (NOZ) did not induce a significant HLN frequency in MRC-Wistar rats. Acetoxime was highly volatile and was not mutagenic in the Ames test under a variety of conditions. The results for acetoxime are of interest because simple oximes are common constituents of oil paints. HLN induction by nitrosodihydrouracil is of interest because, unlike most liver carcinogens, this compound probably does not require metabolic activation and shows only a mild acute hepatoxicity.