Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of auraptene

The modifying effects of auraptene on N-nitrosomethylbenzylamine (NMBA)-ind uced esophageal tumorigenesis were investigated in male F344 rats. At 5 wee ks of age, all animals, except those with the test chemical alone and contr ol rats, received s.c. injections of NMBA (0.5 mg/kg body weight/injection, three times per week) for 5 weeks. At the end of the study (20 weeks), 75% of the rats treated with NMBA alone had esophageal neoplasms (papillomas). However, the groups who received a dose of 500 ppm auraptene during the in itiation phase developed significantly reduced incidence of tumors (39%; P< 0.05). Exposure to auraptene (500 ppm) during the post-initiation phase als o decreased the frequency of the tumors (29%; P<0.01). The reduction of the incidence of severe dysplasia was obtained when auraptene was administered in the post-initiation phase (P<0.05). Cell proliferation in the esophagea l epithelium determined by proliferating cell nuclear antigen (PCNA) was lo wered by auraptene (P<0.01). Blood polyamine contents in rats who received NMBA and the test compound were also smaller than those of rats that receiv ed the carcinogen (P<0.05). These findings suggest that dietary auraptene i s effective in inhibiting the development of esophageal tumors by NMBA when given during the initiation as well as post-initiation phases, and such in hibition is related to suppression of cell proliferation in the esophageal epithelium.