EFFECTS OF MULTIPLE RISK-FACTORS FOR HEPATOCELLULAR-CARCINOMA ON FORMATION OF AFLATOXIN B-1-DNA ADDUCTS

Covalent binding of aflatoxin B-1 (AFB(1)) with hepatic DNA may be a c ritical step in hepatocarcinogenesis. The extent of the AFB(1) binding to DNA may depend on various endogenous factors and concurrent exposu re to other environmental agents, This study was performed to determin e whether any individual characteristics correlated with the formation of AFB(1)-DNA adducts, The major AFB(1)-DNA adduct, AFB(1)-N-7-guanin e, was measured using a high performance liquid chromatographic assay in urine samples from 43 asymptomatic hepatitis B virus surface antige n carriers and 43 noncarriers randomly selected from a cohort study in Taiwan, The total aflatoxin metabolite level was associated with the detection rate of urinary AFB(1)-N-7-guanine adducts in a dose-depende nt manner, The AFB(1)-DNA adduct excreted in the urine was detectable in 60% of individuals who smoked cigarettes but abstained from alcohol , 64% of individuals who had a habit of drinking alcohol but not smoki ng cigarettes, and only 29% of those who neither smoked nor drank alco hol, The association between urinary AFB(1)-DNA adduct level and habit s of smoking cigarettes and drinking alcohol remained statistically si gnificant when adjustment was made for potential confounders, There wa s a significant increase with age for the detection rate of urinary AF B(1)-N-7-guanine adducts, Age and habits of cigarette smoking and alco hol drinking were also found to be associated with a higher percentage of AFB(1)-N-7-guanine in total AFB(1) metabolite excretion, indicatin g an increased activation of AFB(1). No significant association with t he AFB(1)-DNA adduct level was observed for hepatitis B virus surface antigen carrier status, educational level, and ethnicity, These data s uggest a potential role of age, cigarette smoking, and alcohol drinkin g in AFB(1)-induced hepatocarcinogenesis.