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 [3H]thymidine incorporation in exponentially growing cells in a dose-dependent manner. The maximal effect was observed at about 40 and 90% above control at 0.02 mM and 0.05 mM, respectively. The increase induced by 0.02 mM SNAP was abolished by the addition of 0.01 mM oxyhemoglobin, a scavenger of NO. [3H]Thymidine incorporation in stationary cells was 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 cells.