Immunohistochemical localization of prostaglandin endoperoxide G/H synthase isozymes in the normal rat colon epithelium and in 1,2-dimethylhydrazine-induced colon tumours

Objectives. Prostaglandin endoperoxide G/H synthase (PGHS) is a potential target for colon cancer chemoprevention. The aims of this study were to determine if the localization of PGHS isozymes is altered early in 1,2-dimethylhydrazine (DMH)-induced rat colon tumorigenesis and to characterize PGHS isozyme localization in DMH-induced colon tumours. Methods. Male Sprague-Dawley rats were injected once a week for 8 weeks with the colon carcinogen DMH or vehicle and then sacrificed at 9 or 30 weeks. Immunohistochemical detection of PGHS isozymes was performed in normal appearing colonic mucosa and colon tumours. Results. At both time points, in normal appearing colon, PGHS-1 was localized in vascular endothelial cells, smooth muscle cells, and specific cells in the lamina propria, while PGHS-2 localization was limited to a few scattered cells at the periphery of lymphatic nodules. However, both isozymes were localized to carcinoma and stromal cells of DMH-induced colon tumours. Conclusions. PGHS-1 is the predominant isozyme in the rat colon, and PGHS-2 is selectively upregulated in DMH-induced colon tumours.