Modulation of the metabolism of the carcinogen PhIP in rats by cruciferous and apiaceous vegetables

Abstract

Cruciferous and apiaceous vegetables modulate biotransformation enzymes that activate and detoxify carcinogens and may be chemopreventive. Here, we determined in rats the effects of these vegetables supplemented alone or in combination on activation and detoxification of PhIP (2‐amino‐1‐methyl‐6‐phenylimidazo [4,5‐b]pyridine; a carcinogen found in char‐grilled meat). For 7 days we fed male Wistar rats AIN‐93G diet, cruciferous diet (21% cruciferous, wt/wt), apiaceous diet (21% apiaceous vegetables), or combination diet (10.5% each cruciferous and apiaceous vegetables). On day 6, we injected rats with PhIP (10 mg/kg body weight), collected urine for 24 hr, then collected tissues. The cruciferous diet increased liver CYP1A1 and CYP1A2 activities (p < 0.05); these activities were not changed by the other diets. Using a metabolomics approach and UPLC‐TOFMS, urinary PhIP metabolites were analyzed. Consistent with the CYP1A induction, the cruciferous diet increased N2‐OH‐PhIP and 4′‐OH‐PhIP. The apiaceous diet decreased 5‐OH‐PhIP, a biomarker of PhIP‐DNA adducts. The apiaceous diet increased methylated PhIP metabolites. We detected a novel methylated PhIP metabolite not previously reported in rats and in much higher abundance than reported in mice. Apiaceous may enhance detoxification by increasing methylation; the importance of methylation in PhIP detoxification warrants further investigation.Grant Funding Source : Healthy Foods, Healthy Lives Institute, University of Minnesota