NITRIC-OXIDE SYNTHASE ACTIVITY AND EXPRESSION IN HUMAN COLORECTAL-CANCER

The present study investigated the activity and cellular localization of individual isoenzymes of nitric oxide synthase (NOS) using immunohi stochemistry and the [H-3]citrulline assay in normal colorectal epithe lia and neoplastic tissue, Intracellular localization of isoenzymes of NOS was detectable by immunohistochemistry in normal epithelial cells , Colorectal adenocarcinomas had a marked reduction of both inducible NOS (iNOS) and constitutive NOS (cNOS) expression, Expression of iNOS was completely absent in tumour cells (P < 0.0001), while cNOS was red uced in 66% and absent in 34% of tumours studied when compared with co ntrols (P < 0.0001), NOS activity using the [H-3]citrulline assay was detectable in normal epithelium and was found to be reduced in tumours (P < 0.001), In addition, colonic adenomas had reduced iNOS but not c NOS expression when compared with controls (P < 0.003 and P = 0.39 res pectively), We conclude that NOS is present and active within the epit helium of the normal colon, with localization of the individual isoenz ymes, Furthermore, there was loss of activity and expression of indivi dual isoenzymes in colonic neoplasms.