Weak enhancing effects of simultaneous ethanol administration on chemically induced rat esophageal tumorigenesis.
Excessive alcohol consumption is associated epidemiologically with an elevated risk of esophageal cancer. In this study, we examined the effects of simultaneous administration of ethanol on N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis. Groups 1-3 were treated with NMBA at a dose of 0.5 mg/kg body weight (high dose), and groups 4-6 received a dose of 0.1 mg/kg body weight (low dose), by s.c.-injection, 3 times per week for the first 5 weeks. Groups 1 and 4 were given ethanol free water as controls. Groups 2 and 5 were treated with 10% ethanol in their drinking water only at the time of NMBA treatment, while groups 3 and 6 were administrated the supplement continuously up to the end of the experiment. Macroscopically, with high dose NMBA-initiation, simultaneous 5-week and continuous 24-week ethanol administration demonstrated a tendency to increase the incidence and multiplicity of tumors, and also microscopically the multiplicity of papillary hyperplasias. In low dose groups, the incidence of esophageal papillary hyperplasias was significantly increased by continuous 24-week ethanol administration. Immunohistochemistry, proliferating cell nuclear antigen (PCNA) positive indices tended to be increased in tumors by simultaneous 5-week and continuous 24-week ethanol administration, but cyclin D1 expression was not affected. These data suggest that simultaneous ethanol administration have weak enhancing effects, and also promoting effects in post-initiation phase is present on NMBA-induced rat tumorigenesis.
Kaneko
Masahiro
M
Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Morimura
Keiichirou
K
Nishikawa
Takayuki
T
Wanibuchi
Hideki
H
Osugi
Harushi
H
Kinoshita
Hiroaki
H
Koide
Akihiro
A
Mori
Yukio
Y
Fukishima
Shoji
S
D000428:Alcohol Drinking; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D002455:Cell Division; D019938:Cyclin D1 / Q000096:biosynthesis; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives*; D004938:Esophageal Neoplasms / Q000139:chemically induced*; D000431:Ethanol; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D009929:Organ Size / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D051381:Rats; D012997:Solvents; D013997:Time Factors
D002273:Carcinogens; D018809:Proliferating Cell Nuclear Antigen; D012997:Solvents; D019938:Cyclin D1; D000431:Ethanol; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine