K. Kawabata et al., Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of 1 '-acetoxychavicol acetate, JPN J CANC, 91(2), 2000, pp. 148-155
The modifying effects of 1'-acetoxychavicol acetate (ACA) on N-nitrosomethy
lbenzylamine (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 th
e termination of the study (20 weeks), 75% of rats treated with NR IBA alon
e had esophageal neoplasms (papillomas), However, the groups given a dose o
f 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 o
r 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 developme
nt of esophageal tumors by NMBA when given during the initiation or post-in
itiation phase, and such inhibition is related to suppression of cell proli
feration in the esophageal epithelium.