IMMUNOHISTOCHEMICAL LOCALIZATION OF PROSTAGLANDIN ENDOPEROXIDE G H SYNTHASE ISOZYMES IN THE NORMAL RAT COLON EPITHELIUM AND IN 1,2-DIMETHYLHYDRAZINE-INDUCED COLON TUMORS/

Objectives Prostaglandin endoperoxide G/H synthase (PGHS) is a potenti al target for colon cancer chemoprevention. The aims of this study wer e to determine if the localization of PGHS isozymes is altered early i n 1,2-dimethylhydrazine (DMH)-induced rat colon tumorigenesis and to c haracterize PGHS isozyme localization in DMH-induced colon tumours. Me thods Male Sprague-Dawley rats were injected once a week for 8 weeks w ith the colon carcinogen DMH or vehicle and then sacrificed at 9 or 30 weeks. Immunohistochemical detection of PGHS isozymes was performed i n normal appearing colonic mucosa and colon tumours. Results At both t ime points, in normal appearing colon, PGHS-1 was localized in vascula r endothelial cells, smooth muscle cells, and specific cells in the la mina propria, while PGHS-2 localization was limited to a few scattered cells at the periphery of lymphatic modules. However, both isozymes w ere localized to carcinoma and stromal cells of DMH-induced colon tumo urs. Conclusions PGHS-1 is the predominant isozyme in the rat colon, a nd PGHS-2 is selectively upregulated in DMH-induced colon tumours.