Tissue norepinephrine depletion as a mechanism for cysteamine inhibition of colon carcinogenesis induced by azoxymethane in Wistar rats.
The effects of cysteamine (2-aminoethanethiol hydrochloride) on the incidence, number and histology of colon tumors induced by azoxymethane (AOM), and on the norepinephrine concentration in the colon wall tissue and the labelling indices of colon mucosa and colon cancers were investigated in Wistar rats. Rats received 10 weekly injections of 7.4 mg/kg body weight of AOM and alternate-day subcutaneous injections of 25 mg/kg of cysteamine in 0.9% NaCl solution until the end of the experiment. At week 40, prolonged administration of cysteamine significantly reduced the incidence and number of colon tumors. Histologically, the adenocarcinomas that did develop in rats treated with cysteamine exhibited high mucin-producing activity. Administration of cysteamine caused significant decreases in the norepinephrine concentration in colon tissue and in the labelling indices of colon mucosa and cancers. Our findings indicate that cysteamine inhibits the development of colon tumors. This action may be related to its effect in decreasing norepinephrine concentration in the colon wall tissues and subsequently in decreasing proliferation of colon cancer cells.
Tatsuta
M
M
Department of Gastrointestinal Oncology, Center for Adult Diseases, Osaka, Japan.
Iishi
H
H
Baba
M
M
Taniguchi
H
H
D000230:Adenocarcinoma / Q000139:chemically induced; D000236:Adenoma / Q000139:chemically induced; D000818:Animals; D001397:Azoxymethane / Q000494:pharmacology; D002277:Carcinoma / Q000139:chemically induced*; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000139:chemically induced*; D003543:Cysteamine / Q000494:pharmacology*; D005755:Gastrins / Q000097:blood; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D005755:Gastrins; D003543:Cysteamine; D001397:Azoxymethane; D009638:Norepinephrine