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Cancer Prevention Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104, Japan
Nitric oxide (NO) is an important bioregulatory mediator involved in a variety of biological processes under both physiological and pathological conditions. To assess whether NO production is altered in colon carcinogenesis, the expression levels and localization of two isoforms of NO synthase, inducible NO synthase (iNOS) and endothelial constitutive NO synthase (eNOS), were examined by immunoblot and immunohistochemical methods in normal colonic mucosa and colon carcinomas induced by azoxymethane in male F344 rats. All colon carcinoma tissues examined were found to have an increased expression of iNOS and eNOS proteins as compared to normal colonic mucosa. In particular, the pronounced staining of iNOS protein localized to the luminal surface of carcinoma epithelial cells was not detectable in normal colon epithelium. The neovasculature in tumor tissues also demonstrated intense eNOS immunoreactivity in endothelial cells. These findings indicate that NO production is markedly elevated in azoxymethane-induced rat colon carcinomas, suggesting that regulatory pathways involving this mediator have some biological relevance to colon carcinogenesis in this model.
1 Supported in part by grants-in-aid for cancer research from the Ministry of Health and Welfare and from the Ministry of Education, Science, Sports and Culture, Japan, a grant-in-aid from the Ministry of Health and Welfare for the Second-Term Comprehensive 10-Year Strategy for Cancer Control, Japan, and a grant from the Sankyo Foundation of Life Science.
2 To whom requests for reprints should be addressed.
Received 1/22/97. Accepted 2/14/97.
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