K. Kawabata et al., Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of auraptene, J EXP CL C, 19(1), 2000, pp. 45-52
Citations number
39
Categorie Soggetti
Oncology
Journal title
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
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.