Organ-dependent modifying effects of caffeine, and two naturally occurringantioxidants alpha-tocopherol and n-tritriacontane-16,18-dione, on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary and coloniccarcinogenesis in female F344 rats

Modifying effects of caffeine, alpha-tocopherol, and n-tritriacontane-16,18 -dione (TTAD) on 2 -amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-in duced mammary and colonic carcinogenesis were investigated in female F344 r ats. Groups of 20 rats, 6 weeks old, were given 0.02% PhIP (in diet) alone, or together with 0.1% caffeine (in drinking water), 0.5% alpha-tocopherol (in diet) or 0.1% TTAD (in diet) for up to 54 weeks. Groups of 10 females r eceiving basal diet or one of the test chemicals without PhIP supplementati on were also maintained. The final combined incidences (adenomas plus adeno carcinomas) and multiplicity (No./rat) of mammary adenomas and adenocarcino mas were significantly lowered in the PhIP plus caffeine group (10%, 0.10) as compared to the PhIP alone value (40%, 0.50). Incidences of mammary tumo rs in the PhIP plus alpha-tocopherol or TTAD groups tended to be decreased while their multiplicities were significantly lowered. With regard to colon tumor development, on the other hand, rats given PhIP plus caffeine exhibi ted an elevated incidence (75% versus 15% in the control), whereas alpha-to copherol and TTAD had no effect. Surprisingly, metabolic activation of PhIP was inhibited by addition of caffeine in an bl vitro assay. The results in dicate that caffeine exerts a potent chemopreventive action against PhIP-in duced mammary carcinogenesis, but acts as a co-carcinogen for PhIP-induced colonic carcinogenesis.