Effect of chronic dietary ethanol consumption on colonic cancer in rats induced by 1,1-dimethylhydrazine.
BACKGROUND
The pathogenetic correlation between chronic alcohol consumption and development of colon cancer is not clear. The role of alcohol abuse in the carcinogenic action of 1,1-dimethylhydrazine (DMH), which induces tumors in the colon, was evaluated.


METHODS
Twenty male rats were fed liquid diets containing ethanol or carbohydrates for 39 weeks. DMH (20 mg/kg body weight, once a week) was injected subcutaneously from the 5th to the 20th week. Pair feeding was stopped at 10:00 am and DMH was administered at 02:00 pm. Ethanol was not detected in the blood at the time of injection. Liquid diets were provided again at 05:00 pm until 10:00 am next day. The animals were killed at the end of the 39th week, and the colons were removed for examination for the number of aberrant crypt foci (ACF) by methylene blue staining. Tissue sections were stained for histology and cytochrome P4502E1 (CYP2E1) expression.


RESULTS
The number of ACF in colons obtained from ethanol-fed rats with DMH was 24 (n=5, 4.4+/-2.5/rat), which was significantly (p<0.001) more than that of the other treated rats: only 3 (n=5, 0.6+/-0.5/rat) in the pair-fed control rats with DMH, and none in the ethanol-fed or control-fed rats without DMH. Cytochrome P4502E1 staining demonstrated marked expression in the colon mucosa from ethanol-fed rats, but not in the pair-fed control rats.


CONCLUSIONS
The increased expression of CYP2E1 induced by chronic ethanol consumption promotes the development of DMH-induced colon cancer.
Hayashi
Nobuhiko
N
Department of Gastroenterology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Tsutsumi
Mikihiro
M
Fukura
Masayuki
M
Yano
Hirokazu
H
Tsuchishima
Mutsumi
M
Takase
Shujiro
S
D000437:Alcoholism / Q000473:pathology*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000473:pathology; D003043:Cocarcinogenesis; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology*; D019392:Cytochrome P-450 CYP2E1 / Q000032:analysis; D004127:Dimethylhydrazines / Q000633:toxicity*; D000431:Ethanol / Q000633:toxicity*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D002273:Carcinogens; D004127:Dimethylhydrazines; D000431:Ethanol; C013958:dimazine; D019392:Cytochrome P-450 CYP2E1