PROMOTION OF PROLIFERATION OF MURINE BALB C3T3 FIBROBLASTS MEDIATED BY NITRIC-OXIDE AT LOWER CONCENTRATIONS/

This study showed that nitric oxide (NO)-generating S-nitrosothiols, S -nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (GSNO), increased proliferation of BALB/c 3T3 (clone A31-1-1) fibroblasts in vitro. Treatment with SNAP at a relatively low concentration (0.005-0. 02 mM) induced an increase in cell number compared to control. SNAP (0 .005-0.02 mM) and GSNO (0.025-0.05 mM) both showed an increase of [H-3 ]thymidine incorporation in exponentially growing cells in a dose-depe ndent manner. The maximal effect was observed at about 40 and 90% abov e control at 0.02 mM and 0.05 mM, respectively. The increase induced b y 0.02 mM SNAP was abolished by the addition of 0.01 mM oxyhemoglobin, a scavenger of NO. [3H]Thymidine incorporation in stationary cells wa s also increased by SNAP. In addition, 0.02 mM SNAP produced a 1.8-3.2 -fold increase of thymidine kinase activity in exponentially growing c ells.