Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of 1′-acetoxychavicol acetate

The modifying effects of 1'-acetoxychavicol acetate (ACA) on N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis, were investigated in male F344 rats. At 5 weeks of age, all test animals, except those given the test chemical alone, and the control rats received s.c. injections of NMBA (0.5 mg/kg body weight/injection, three times per week) for 5 weeks. At the termination of the study (20 weeks), 75% of rats treated with NR IBA alone had esophageal neoplasms (papillomas), However, the groups given a dose of 500 ppm ACA during the initiation phase developed a significantly reduced incidence of tumors (29%; P < 0.01). Exposure to ACA (500 ppm) during the post-initiation phase also decreased the frequency of the tumors (38%; P < 0.05). A reduction of the incidence of preneoplastic lesions (hyperplasia or dysplasia) was obtained when ACA was administered in the initiation phase (P < 0,01), Cell proliferation in the esophageal epithelium. determined by assay of proliferating cell nuclear antigen (PCNA), was lowered by ACA (P < 0.05). Blood polyamine contents in rats given NMBA and the test compound were also smaller than those of rats given the carcinogen (P < 0,05), These findings suggest that dietary ACA is effective in inhibiting the development of esophageal tumors by NMBA when given during the initiation or post-initiation phase, and such inhibition is related to suppression of cell proliferation in the esophageal epithelium.