Plasma antioxidant vitamins, chronic hepatitis B virus infection and urinary aflatoxin B1-DNA adducts in healthy males

Epidemiological evidence indicates that aflatoxin B1 (AFB1) intake isassociated with an increased risk of hepatocellular carcinoma (HCC). Thehepatocarcinogenesis is initiated by covalent binding of AFB1 to cellularDNA. To determine whether nutritional factors and hormonal status mayinfluence the binding of AFB1 to hepatic DNA, a cross- sectional study wasperformed on a total of 42 male asymptomatic hepatitis B surface antigen(HBsAg) carriers and 43 male non-carriers in a cohort study on themultistage development of HCC in Taiwan. The major AFB1-DNA adduct in vivo,AFB1-N7-guanine, was measured by high- performance liquid chromatography inurine. Urinary AFB1-N7-guanine was detectable in 40% of the subjects. HBsAgcarriers had a higher detection rate of urinary AFB1-DNA adducts thannon-carriers and the difference was statistically significant aftermultivariate adjustment. After taking into account the total AFB1 urinarymetabolite level, chronic HBsAg carrier status, and other potentialconfounders, plasma levels of cholesterol, alpha-tocopherol, and alpha- andbeta-carotene were positively associated with the detection rate of theAFB1-DNA adducts in a dose-dependent manner, whereas plasma lycopene levelwas inversely related to the presence of the adducts in urine. Theassociation of urinary AFB1-DNA adducts with the plasma levels ofcholesterol, alpha-tocopherol, lycopene, and alpha- and beta-carotene wasobserved at both low and high exposure levels of AFB1. There was asynergistic interaction of plasma alpha-tocopherol with alpha- and beta-carotene on the adduct levels. No association with the adducts was foundfor plasma levels of retinol and testosterone. This study demonstrateddifferent associations of antioxidant vitamins with AFB1- DNA adductformation. The data consistent with our previous finding in culturedwoodchuck hepatocytes that alpha-tocopherol and beta-carotene enhancedAFB1-DNA adduct formation suggest that prospective investigation of therelationship between plasma micronutrients and risk of AFB1-related HCC iswarranted.