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 stage was investigated in the N-nitrosobis(2-oxopropyl)amine (BOP)-initiated hamster tumorigenesis model. Ninety male 5-week-old hamsters were divided into three groups, each consisting of 30 animals, and s.c. injected with 20 mg / kg of BOP twice with a one-week interval. Groups 1 through 3 were fed diet supplemented with ACA at concentrations of 500, 100 and 0 ppm, respectively, for 3 weeks starting one week before the first carcinogen application. At the termination of experimental week 54, the total incidence and multiplicity 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 the group 3 values (50.0% and 0.7 < 0.8). The ACA treatments also showed a tendency 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-induced cholangiocarcinogenesis in hamsters. Taken together with previous findings of inhibited colon, oral and skin carcinogenesis in rats and mice, they suggest that ACA is a candidate chemopreventive agent with a wide spectrum of activity.