Plasma antioxidant vitamins, chronic hepatitis B virus infection and urinary aflatoxin B1-DNA adducts in healthy males |
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Authors: | Yu MW; Chiang YC; Lien JP; Chen CJ |
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Institution: | School of Public Health, College of Public Health, National Taiwan University, Taipei. |
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Abstract: | Epidemiological evidence indicates that aflatoxin B1 (AFB1) intake is
associated with an increased risk of hepatocellular carcinoma (HCC). The
hepatocarcinogenesis is initiated by covalent binding of AFB1 to cellular
DNA. To determine whether nutritional factors and hormonal status may
influence the binding of AFB1 to hepatic DNA, a cross- sectional study was
performed on a total of 42 male asymptomatic hepatitis B surface antigen
(HBsAg) carriers and 43 male non-carriers in a cohort study on the
multistage development of HCC in Taiwan. The major AFB1-DNA adduct in vivo,
AFB1-N7-guanine, was measured by high- performance liquid chromatography in
urine. Urinary AFB1-N7-guanine was detectable in 40% of the subjects. HBsAg
carriers had a higher detection rate of urinary AFB1-DNA adducts than
non-carriers and the difference was statistically significant after
multivariate adjustment. After taking into account the total AFB1 urinary
metabolite level, chronic HBsAg carrier status, and other potential
confounders, plasma levels of cholesterol, alpha-tocopherol, and alpha- and
beta-carotene were positively associated with the detection rate of the
AFB1-DNA adducts in a dose-dependent manner, whereas plasma lycopene level
was inversely related to the presence of the adducts in urine. The
association of urinary AFB1-DNA adducts with the plasma levels of
cholesterol, alpha-tocopherol, lycopene, and alpha- and beta-carotene was
observed at both low and high exposure levels of AFB1. There was a
synergistic interaction of plasma alpha-tocopherol with alpha- and beta-
carotene on the adduct levels. No association with the adducts was found
for plasma levels of retinol and testosterone. This study demonstrated
different associations of antioxidant vitamins with AFB1- DNA adduct
formation. The data consistent with our previous finding in cultured
woodchuck hepatocytes that alpha-tocopherol and beta-carotene enhanced
AFB1-DNA adduct formation suggest that prospective investigation of the
relationship between plasma micronutrients and risk of AFB1-related HCC is
warranted.
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