Chemoprevention of Aflatoxin B₁-Initiated and Carbon Tetrachloride-Promoted Hepatocarcinogenesis in the Rat by Green Tea

Abstract

Chemoprevention of hepatocarcinogenesis by green tea (GT) has been examined in young male Fischer rats fed AIN-76A diet with aflatoxin B₁ (AFB₁) and CC₄ as the initiator and promoter, respectively. Animals were administered AFB₁(0.25 mg/kg body wt ip) twice a week for 2 weeks, and 2 weeks later, CCl4 was injected (0.8 ml/kg body wt ip) once per week for 11 weeks. Rats given 0.5% GT in their drinking water before and during initiation (0-4 wk) or during promotion (6-16 wk) or throughout the experimental period were sacrificed 24 hours after the last dose of CCl4. Bromodeoxyuridine incorporation as a measure of cell proliferation and glutathione S-transferase placental form- and g-glutamyl transpeptidase-positive hepatic foci were analyzed by histochemical methods. Feeding of GT during initiation or promotion inhibited the number of glutathione S-transferase placental form- and γ-glutamyl transpeptidase-positive hepatic foci by 30-40% and the area and volume by 50%. GT treatment throughout the period inhibited the number of both types of hepatic foci by 60% and the area and volume by 75-80%. Cell proliferation was inhibited 35% by GT given during promotion, whereas inhibition was 65% when GT was given during initiation or throughout the period. These results indicate that GT feeding inhibits initiation and promotion steps of AFB₁; hepatocarcinogenesis and that the inhibition of cell proliferation is responsible for the inhibition of promotion.