Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of auraptene.
The modifying effects of auraptene on N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis were investigated in male F344 rats. At 5 weeks of age, all animals, except those with the test chemical alone and control 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 initiation phase developed significantly reduced incidence of tumors (39%; P<0.05). Exposure to auraptene (500 ppm) during the post-initiation phase also 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 esophageal epithelium determined by proliferating cell nuclear antigen (PCNA) was lowered 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 received the carcinogen (P<0.05). These findings suggest that dietary auraptene is effective in inhibiting the development of esophageal tumors by NMBA when given during the initiation as well as post-initiation phases, and such inhibition is related to suppression of cell proliferation in the esophageal epithelium.
Kawabata
K
K
First Dept. of Pathology, Gifu University School of Medicine, Japan.
Tanaka
T
T
Yamamoto
T
T
Hara
A
A
Murakami
A
A
Koshimizu
K
K
Ohigashi
H
H
Stoner
G D
GD
Mori
H
H
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D002273:Carcinogens / Q000633:toxicity*; D003374:Coumarins / Q000008:administration & dosage*; D004032:Diet; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000633:toxicity; D004938:Esophageal Neoplasms / Q000139:chemically induced* / Q000517:prevention & control*; D015994:Incidence; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D003374:Coumarins; C014707:nitrosobenzylmethylamine; C105832:aurapten; D004128:Dimethylnitrosamine