NITRIC-OXIDE SYNTHASE ACTIVITY IN HUMAN GYNECOLOGICAL CANCER

Nitric oxide is generated by the NO synthases, a family of isoenzymes expressed in a wide range of mammalian cells. In the vascular and nerv ous systems distinct isoforms generate NO to act as a signal transduct ion mechanism. The isoform induced by cytkines, on the other hand, pro vides a sustained release of NO which mediates some cytotoxic and cyto static effects of the immune system. Solid tumors are a heterogeneous population of cell types, including tumor, vascular and infiltrating i mmune cells. Studies in vitro show that NO synthase can be present in many of these cells. However, its presence in situ in solid human tumo rs has not been reported. In this study, we have investigated NO synth ase activity and its cellular localization in malignant and nonmaligna nt human gynecological tissue. Nitric oxide synthase activity was obse rved in malignant tissue, was highest (greater than or equal to 250 pm ol/min/g tissue) in poorly differentiated tumors, and was below detect able levels in normal gynecological tissue. Furthermore, investigation s with a polyclonal NO sgnthase antibody revealed immunoreactivity onl y in malignant tissue. This was associated with NO synthase activity a nd localized to tumor cells. Thus NO synthase is present in human gyne cological tumors, and its presence seems to correlate inversely with t he differentiation of the tumor.