Suppression of N‐Nitrosomethylbenzylamine‐induced Rat Esophageal Tumorigenesis by Dietary Feeding of 1′‐Acetoxychavicol Acetate

Abstract

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 NMBA 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.