Inhibition of aflatoxin B1-induced initiation of hepatocarcinogenesis in the rat by green tea

Abstract

Several studies have demonstrated that green tea (GT) inhibits various chemically induced cancers in experimental animals. In the present study, effect of GT has been examined on the initiation of aflatoxin B1 (AFB1)-induced hepatocarcinogenesis in the rat. Young male Fischer rats were given AIN-76A diet with or without 0.5% instant GT powder in their drinking water for 2 or 4 weeks. Initiation was examined by hepatic AFB1-DNA binding in vivo, AFB1 metabolism in vitro and by the appearance of AFB1-induced glutathione S-transferase placental form (GST-P)-positive hepatocytes detected by immunohistochemical method. There was no influence of GT feeding on microsome-mediated AFB1 binding to exogenous DNA. However, GT feeding enhanced microsome-mediated formation of non-toxic hydroxylated metabolites of AFB1 by 2-3-fold. Hepatic nuclear AFB1-DNA binding in vivo was significantly inhibited by about 20-30% in animals pretreated with GT: AFB1-induced GST-P positive single hepatocytes were inhibited significantly by 60-70% in rats pretreated with GT. These results suggest that feeding of GT inhibits initiation of AFB1-induced hepatocarcinogenesis in the rat by modulation of AFB1 metabolism, thereby inhibiting AFB1-DNA binding and AFB1-induced GST-P-positive hepatocytes.