Inhibitory effects of 1 '-acetoxychavicol acetate on N-nitrosobis(2-oxopropyl)-amine-induced initiation of cholangiocarcinogenesis in Syrian hamsters

The influence of 1'-acetoxychavicol acetate (ACA) during the initiation sta ge was investigated in the N-nitrosobis(2-oxopropyl)amine (BOP)-initiated h amster tumorigenesis model, Ninety male 5-week-old hamsters were divided in to three groups, each consisting of 30 animals, and s.c, injected with 20 m g/kg of BOP twice with a one-week interval. Groups 1 through 3 were fed die t supplemented with ACA at concentrations of 500, 100 and 0 ppm, respective ly, for 3 weeks starting one week before the first carcinogen application. At the termination of experimental week 54, the total incidence and multipl icity of cholangiocellular adenomas and carcinomas in group 1 (17.9% and 0. 3+/-0.9) were significantly (P<0.05 and P<0.01) decreased as compared to th e group 3 values (50.0% and 0.7+/-0.8), The ACA treatments also showed a te ndency to reduce the development of preneoplastic lesions in the pancreas, a main target organ of BOP, although this was not statistically significant . Our results thus indicate that ACA exerts an inhibitory effect on BOP-ind uced cholangiocarcinogenesis in hamsters, Taken together with previous find ings of inhibited colon, oral and skin carcinogenesis in rats and mice, the y suggest that ACA is a candidate chemopreventive agent with a wide spectru m of activity.