Modification by 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) of 3,2′-dimethyl-4-aminobiphenyl (DMAB)-induced rat pancreatic and intestinal tumorigenesis

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been shown to induce marked atrophic changes of exocrine pancreas of rats when given at 400 ppm in diet. On the other hand, 3,2′-dimethyl-4-aminobiphenyl (DMAB) causes pancreatic acinar tumors. Both chemicals also induce intestinal tumors. In the present experiment, the possible promotional effects of PhIP on DMAB-induced carcinogenesis in the rat were investigated with particular attention given to the pancreas and intestine. After initiation with subcutaneous injections of DMAB (150 mg/kg b.w.) once a week for 3 weeks, PhIP was administered in the diet at doses of 200, 100, 25 and 0 ppm from weeks 5 to 40. In a dose-dependent manner, PhIP clearly increased the numbers of basophilic acinar foci and nodules while decreasing development of acidophilic lesions. The incidences of adenocarcinomas of the small intestine but not the colon demonstrated a tendency for an increase with the higher doses of PhIP. The results thus indicated that PhIP administration after DMAB treatment exerts two different effects on pancreatic acinar cell lesions, enhancing the growth of basophilic foci and suppressing that of their acidophilic counterparts. Any influence on alimentary canal tumorigenesis was limited to the small intestine.