PREVENTION BY 1'-ACETOXYCHAVICOL ACETATE OF THE INDUCTION BUT NOT GROWTH OF PUTATIVE PRENEOPLASTIC, GLUTATHIONE-S-TRANSFERASE PLACENTAL FORM-POSITIVE, FOCAL LESIONS IN THE LIVERS OF RATS FED A CHOLINE-DEFICIENT, L-AMINO ACID-DEFINED DIET

The effects of 1'-acetoxychavicol acetate (ACA) on endogenous rat live r carcinogenesis because of chronic feeding of a choline-deficient, L- amino acid-defined (CDAA) diet were examined. Male Fischer 344 rats, 6 weeks old, received the CDAA diet containing ACA at doses of 0, 0,005 , 0.010 and 0.050% for 12 weeks and were then killed. ACA decreased th e numbers of putative preneoplastic, glutathione S-transferase placent al form (GST-P)-positive, focal lesions developing in the livers of ra ts fed the CDAA diet but did not alter their sizes. At the same time, ACA reduced the levels of 8-hydroxyguanine, a parameter of oxidative D NA damage, but did not significantly affect generation of 2-thiobarbit uric acid-reacting substances, indicators of oxidative extra-DNA damag e, or hepatocyte proliferation. Furthermore, ACA did not exert any sig nificant effects on the numbers or sizes of GST-P-positive lesions in the livers of fats when administered between weeks 2 and 8 after initi ation with a single i.p. dose of 200 mg/kg body wt of N-nitrosodiethyl amine. These results indicate that ACA prevents the CDAA diet-associat ed induction of putative preneoplastic lesions by reduction of oxidati ve DNA damage but does not affect their subsequent growth.