The effect of aflatoxin on the HPRT gene, hepatitis B viral infection, and the subsequent development of hepatocellular carcinoma in the People's Republic of China

Few carcinogenic mechanisms involved in the development of HCC are known. Exposure to aflatoxin leads to protein and DNA adduct formation, which may induce DNA mutations, bringing cells a step closer to transformation. To confirm the association between aflatoxin adduct formation and subsequent DNA mutations, the hypoxanthine ribosyl transferase (HPRT) reporter gene was used as a somatic target of DNA damage in cells.; A cross sectional study was conducted in Qidong County, People's Republic of China, to evaluate if aflatoxin albumin adducts are associated with high HPRT mutant frequency. An odds ratio of 19.3 (95% confidence interval: 20, 183) was demonstrated for high HPRT mutation frequency in individuals with high aflatoxin exposure compared to those with low aflatoxin exposure. This association indicates that aflatoxin induces DNA and protein adducts, leading to subsequent DNA damage, which is reflected by mutations in the HPRT gene.; The effect of aflatoxin on HBV-induced HCC was subsequently investigated. HBV serological profiles were assessed to determine whether one's immune response to HBV is altered in the presence of aflatoxin. A case control study was conducted in Haidong County, P.R.C. in a HBsAg seropositive cohort. Five non-HCC controls were matched on age and gender to each HCC case diagnosed between 1989 and 1996. Aflatoxin exposure was determined by aflatoxin albumin adduct levels, and their interactions with hepatitis profiles were assessed. Associations between specific hepatitis B serological profiles (HBsAg, HBsAb, Total HBcAb, IgM HBcAb, HBeAb, and HBeAg) with HCC cases were investigated.; The independent association between aflatoxin and HCC was confirmed in this study (odds ratio: 2.7; 95% CI: 0.9, 8.0). Independent associations between total HBcAb, IgM HBcAb, HBsAb, HCV-Ab and HCC were also demonstrated with odds ratios of 2.7, 2.0, 2.1 and 2.2, respectively. More importantly, dose response relationships were observed between aflatoxin and IgM HBcAb (trend p {dollar}<{dollar} 0.02), and HBeAg (trend p {dollar}<{dollar} 0.01), and HCV (trend p {dollar}<{dollar} 0.20) for increased risks of HCC.; These results indicate that aflatoxin exposure in the presence of specific hepatitis profiles increase the risk for HCC. The results also support the hypothesis that aflatoxin is an immunosuppressant and those with high exposures to aflatoxin are therefore more susceptible to the carcinogenic effects of HBV that lead to HCC.