Induction of hyperplastic liver nodules in hepatectomized rats treated with 3'-methyl-4-dimethylaminoazobenzene, benzo[a]pyrene or phenobarbital before or after exposure to N-2-fluorenylacetamide.

The effects of pre- and post-administration of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB), benzo[a]pyrene (B[a]P), and phenobarbital (PB) on the induction of hyperplastic liver nodules by N-2-fluorenylacetamide (2-FAA) were studied in F344 rats. Rats were given 3'-Me-DAB (0.06% in the diet), B[a]P (80 mg/kg b.wt. x 7, intragastrically) or PB (0.05% in the diet) for 6 weeks before (experimental series I) or after (experimental series II) diet containing 0.02% 2-FAA for 2 weeks, and killed in week 10 of the experiment. The number and total area of hyperplastic nodules per unit area of liver were greatest in rats treated with 3'-Me-DAB in both experimental series. B[a]P significantly increased the induction of hyperplastic nodules in experimental series I and PB significantly increased it in experimental series II. Partial hepatectomy performed during administration of test chemicals enhanced the induction of hyperplastic nodules, especially in experimental series I, and an oral dose of carbon tetrachloride during 2-FAA feeding enhanced it in both experimental series. In the present system, initiating activity of both the hepato- and the non-hepatocarcinogen was detected, and promoting activity of both the hepatocarcinogen and the hepatopromoter was demonstrated.