Gender-Dependent Mechanisms of Alpha-Tocopherol Protection from Benzo[a]pyrene Exposure in Rats

Abstract

Polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene (BP), are environmental pollutants linked to increased disease susceptibilities. Alpha-Tocopherol (aT) supplementation decreases BP-DNA adducts in smokers, particularly women; but the mechanism is unknown. To test the hypothesis that aT protection from BP exposure is gender-dependent, male and female rats received 7 daily subcutaneous (SQ) injections of aT (100 mg aT/ kg body wt) or vehicle, followed by a single ip injection of BP (20 mg/kg, spiked with 3H-BP) on day 9. Urine and bile were collected pre- and post-BP. Plasma and tissues were collected 5 or 24 hr post-BP. aT supplementation increased aT levels in females greater than males. Compared to vehicle, aT supplementation increased total urinary and biliary excretion of BP and/or BP metabolites more than 2.5-fold in females, but decreased total BP and/or BP metabolite excretion in males (p<0.05). SQ aT prevented BP-induced increases in urine 8-isoprostanes (males) and decreased tissue malondialdehyde levels in a tissue- and gender-dependent manner. These data are the first to suggest that aT protection from BP exposure is gender-dependent and occurs by both antioxidant and non-antioxidant mechanisms. Further elucidation of the mechanism(s) of aT protection against PAHs may lead to the development of novel protective strategies for occupational PAH exposures.