Gender‐Dependent Modulation of Benzo[a]pyrene Metabolism and Oxidative Stress by Alpha‐Tocopherol in Rats

Benzo[a]pyrene (BP) is an environmental toxin linked to increased disease susceptibilities. Activated BP metabolites form DNA‐adducts, which are positively associated with cancer risk. α‐Tocopherol (αT) supplementation decreases BP‐DNA adducts in smokers, particularly females; but the mechanism is unknown. To test the hypothesis that αT protects tissues from BP exposure by 1) decreasing oxidative stress and 2) altering BP metabolism/excretion, male/female rats received subcutaneous (SC) αT (100 mg/kg, 7 days) or vehicle followed by 3 H‐BP (20 mg/kg, on day 8). Urine and bile were collected pre‐ and post‐BP; tissue and plasma 24 h post‐BP. SC αT increased tissue αT levels (females > males) and prevented BP‐induced elevation of 8‐isoPGF2α levels (both genders). Compared to vehicle rats, total BP radioactivity decreased in liver and lung of αT males, while increasing in αT females. SC αT increased urinary excretion of BP/BP metabolites (females) and altered bile BP‐metabolite profiles (females), compared to vehicle rats. These data are the first to suggest that αT protection from BP‐damage 1) occurs by antioxidant and non‐antioxidant mechanisms and 2) differs with gender. Supported by NIEHS R21ES015872.