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 0.01mM oxyhemoglobin, a scavenger of NO. [3H]Thymidine incorporation in stationary cells was also increased by SNAP. In addition, 0.02mM SNAP produced a 1.8‐3.2‐fold increase of thymidine kinase activity in exponentially growing cells.