Chemoprevention of aflatoxin B1-initiated and carbon tetrachloride-promoted

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Chemoprevention of aflatoxin B1-initiated and carbon tetrachloride-

promoted hepatocarcinogenesis in the rat by green tea.

Qin G, Ning Y, Lotlikar PD.

Fels Institute for Cancer Research and Molecular Biology and the

Department of Biochemistry, Temple University School of Medicine,

Philadelphia, PA 19140, USA.

Chemoprevention of hepatocarcinogenesis by green tea (GT) has been

examined in young male Fischer rats fed AIN-76A diet with aflatoxin

B1 (AFB1) and CCl4 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

placentalform- and gamma-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 gamma-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.