Promotion of chemically induced rat esophageal tumorigenesis with post-initiation ethanol modification.
Post-initiation ethanol modification on N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal carcinogenesis model was investigated in male, 6-week-old, F344 rats that received s.c. injections, 3 times per week, of 0.5 mg/kg NMBA for the first 5 weeks and then were treated with 0% (Group 1), 3.3% (Group 2), and 10% (Group 3) ethanol in the drinking water for up to 20 weeks. Group 4 received 10% ethanol without NMBA administration and Group 5 was maintained without any chemical treatment. There were no statistical differences in the incidence and multiplicity of esophageal tumors among Groups 1 to 3. However, the multiplicity of hyperplasias was statistically greater in Group 3 than in Groups 1 or 2. Esophageal epithelia of all rats in Groups 4 and 5 demonstrated a normal histology. BrdU labelling indices of tumors and hyperplasias in NMBA-treated groups were essentially similar, although cycline D1 was overexpressed to a greater extent in tumors and also hyperplasias of Group 3 than in Groups 1 or 2. The results indicated ethanol to exert weak promotion effects through cycline D1 overexpression on rat esophageal tumorigenesis initiated with NMBA.
Morimura
K
K
Department of Pathology Osaka City University Medical School, Asahi-machi, Abeno-ku, Osaka, Japan.
Hori
T
T
Kaneko
M
M
Nishikawa
T
T
Nishikawa
A
A
Wanibuchi
H
H
Takada
N
N
Osugi
H
H
Fukushima
S
S
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002273:Carcinogens; D019938:Cyclin D1 / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives; D018450:Disease Progression; D004848:Epithelium / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000139:chemically induced*; D004947:Esophagus / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D006965:Hyperplasia; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D019938:Cyclin D1; D000431:Ethanol; C014707:nitrosobenzylmethylamine; D001973:Bromodeoxyuridine; D004128:Dimethylnitrosamine