Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of 1'-acetoxychavicol acetate.
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.
Kawabata
K
K
First Department of Pathology, Gifu University School of Medicine. kuni-ka@c.c.gifu-u.ac.jp
Tanaka
T
T
Yamamoto
T
T
Ushida
J
J
Hara
A
A
Murakami
A
A
Koshimizu
K
K
Ohigashi
H
H
Stoner
G D
GD
Mori
H
H
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001592:Benzyl Alcohols; D015317:Biogenic Polyamines / Q000032:analysis; D018736:DNA Adducts / Q000032:analysis; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000633:toxicity; D004938:Esophageal Neoplasms / Q000517:prevention & control*; D008297:Male; D011230:Precancerous Conditions / Q000517:prevention & control; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D013729:Terpenes / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D001592:Benzyl Alcohols; D015317:Biogenic Polyamines; D018736:DNA Adducts; D018809:Proliferating Cell Nuclear Antigen; D013729:Terpenes; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine; C047948:1'-acetoxychavicol acetate