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An in vitro study was performed using tumor necrosis factor-alpha (TNF alpha) to determine the mechanism by which TNF alpha inhibits the activity of the nitric oxide (NO) synthase system in the effusion of patients with breast cancer. Murine NIH/3T3 fibroblasts were incubated with various concentrations of TNF alpha for 24 hours in the presence or absence of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of the activity of the NO synthase system. The activity of the NO synthase system in the murine effusions was determined by the capacity of the cells to inhibit the conversion of 14C-L-arginine to 14C-L-citrulline. The results showed that TNF alpha inhibited the activity of the NO synthase system in a dose-dependent manner. Treatment with L-NMMA enhanced the effect of TNF alpha on the activity of the NO synthase system. In the effusion of patients with breast cancer, TNF alpha inhibited the activity of the NO synthase system. This inhibition was independent of production of NO.
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