NITRIC-OXIDE SYNTHASE ACTIVITY IN FRESH CELLS FROM OVARIAN TUMOR-TISSUE - RELATIONSHIP OF ENZYME-ACTIVITY WITH CLINICAL-PARAMETERS OF PATIENTS WITH OVARIAN-CANCER

Recent studies suggest a dual role for nitric oxide (NO) in tumour bio logy. High concentrations of NO can mediate tumouricidal activity, whe reas lower concentrations have been shown to promote tumour growth. In this study, NO synthase (NOS) activity was investigated in cells that were prepared from tissue from primary and metastatic sires and from malignant effusions in 41 cases of suspected ovarian cancer. NO biosyn thesis, determined by nitrite + nitrate (NOx) accumulation in medium f rom cultured cells prepared from disaggregated rumours or effusions an d indicative of the inducible NO synthase isoform, was detected in 37% of the cases investigated (range 10.2-114 mu M). There was a signific ant relationship between NOx and tumour differentiation (P = 0.014), w ith NOx being significantly higher for the more differentiated rumours . NOS activity, determined by the conversion of radiolabelled L-argini ne to citrulline by tissue or cell extracts, was detected in 29% of ca ses (range 0.9-6.9 pmol/min per mg of protein), with all samples teste d being moderately or poorly differentiated. Seventy percent of this a ctivity was calcium dependent, indicative of constitutive NOS isoforms . Morphological and immunohistochemical assessment of tumour samples i ndicated a significant relationship between high macrophage content an d NOS activity (as NOx biosynthesis) (r(s) = 0.726, N = 16, P < 0.01). The relationship between NOS expression, immune response, and disease progression is complex and not simply dependent on the differentiatio n status of ovarian cancer. BIOCHEM PHARMACOL 56;10:1365-1370, 1998. ( C) 1998 Elsevier Science Inc.