Route-dependent, organ-specific effects of carcinogens on induction of hyperplastic liver nodules in rats

The inductions of hyperplastic liver nodules (HN) by four carcinogens were examined by their administration continuously and repeatedly by intragastric (i.g.), intraperitoneal (i.p.), intravenous (i.v.) and/or subcutaneous (s.c.) injections before (initiation stage) or after (promotion stage) exposure to N-2-fluorenylacetamide (2-FAA) in male F344 rats. Diethylnitrosamine (DEN), a water-soluble hepatocarcinogen, and 3'-methyl-4-dimethylaminobenzene (3'-Me-DAB), a water-insoluble hepatocarcinogen, markedly increased development of HN when administered by any route in both stages. However, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a water-soluble non-hepatocarcinogen, and benzo[a]pyrene (B[a]P), a water-insoluble non-hepatocarcinogen, increased HN slightly by all or some of the routes of application only in the initiation stage. The influence of the administration route was more evident with water-insoluble compounds in the promotion stage and with non-hepatocarcinogens in the initiation stage.