Organ dependent enhancement of rat 3,2 '-dimethyl-4-aminobiphenyl (DMAB) carcinogenesis by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP): positive effects on the intestine but not the prostate

In order to evaluate tumor enhancing effects of the heterocyclic carcinogen , 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), doses of 100 and 300 p.p.m. PhIP were given for 40 weeks to male F344 rats, which initially received 3,2 ' -dimethyl-4-aminobiphenyl (DMAB). DMAB shows a similar carci nogenic organ spectrum to that of PhIP, including the prostate and colon. P hIP alone at a dose of 300 p.p.m. resulted in the development of prostate a nd intestine cancers. Furthermore, among the DMAB-treated group, enhancemen t of intestinal carcinogenesis by 300 p.p.m. PhIP was observed. However, no prostate enhancement was demonstrated in the DMAB + PhIP group. Since PhIP -DNA adduct formation in the prostate epithelial cells in a satellite exper iment was not affected by pre-treatment with DMAB, it is speculated that th e contradictory findings between the intestine and prostate may be due to t he specific biological effects of PhIP. Taking into account previous data, that PhIP clearly enhanced rat 1,2-dimethylhydrazine-initiated colon tumori genesis, the potential of PhIP to enhance colon carcinogenesis may be initi ator dependent.