GLUTATHIONE-S-TRANSFERASE EXPRESSION IN HEPATITIS-B VIRUS-ASSOCIATED HUMAN HEPATOCELLULAR CARCINOGENESIS

Hepatitis B virus (HBV) and aflatoxin B-1 represent the main risk fact ors for the development of hepatocellular carcinoma (HCC) in areas end emic for liver cancer. The glutathione S-transferases (GSTs) are a fam ily of Phase II detoxification enzymes that catalyze the conjugation o f a wide variety of endogenous and exogenous toxins, including aflatox in B-1, with glutathione. This study characterizes the GST isoenzyme c omposition (alpha, mu, and pi) of both HBV-infected normal hepatic tis sues and HCCs. Analysis of matched pairs of hepatic tissue (normal and tumor) from 32 HCC patients indicated that total GST activity was sig nificantly higher in normal tissues than in tumor tissues, although th e percentage of samples expressing GST alpha and pi was equivalent. GS T mu was detected by Western blot in the normal tissue from 87.5% of t he subjects possessing the GST M1 gene but only 28.6% of the correspon ding tumor tissues. The GST activity of normal tissue from GST M1 null patients was significantly decreased as compared to that of subjects possessing the GST M1 gene (264.6 and 422.2 nmol/min/mg, respectively; P = 0.005). GST pi appeared to be overexpressed in the normal tissue of GST M1 null patients, a potential compensatory effect. Patients pos itive for HBV DNA had significantly lower GST activity than those who were HBV negative (302.1 versus 450.0 nmol/min/mg, respectively; P = 0 .02). These results suggest that cellular protection within the human liver is compromised by HBV infection and further decreased during hep atocellular tumorigenesis.