NITRIC-OXIDE AND SUPEROXIDE IN CULTURED-CELLS - LIMITED PRODUCTION AND INFLUENCE ON DNA-SYNTHESIS

The ability of superoxide (O2-) and NO to influence DNA synthesis, as estimated by [H-3]thymidine incorporation in logarithmically growing cells, was evaluated in three human cell types: embryonic lung fibroblasts, skin fibroblasts, and mesangial cells. Nontoxic rates of O2- generation (0.2 nM/min-0.2 muM/min) only slightly stimulated DNA synthesis in mesangial cells (10-13% increase) and did not affect fibroblast DNA synthesis. Nontoxic rates of NO generation (0.1-10 muM/min) also had only limited effects, inhibiting DNA synthesis in lung and skin fibroblasts slightly (10-20% decrease) but not affecting mesangial cells. In all three cell types, neither O2- nor NO was generated at high enough endogenous rates to support an autocrinic regulation of DNA synthesis. This and other lines of evidence indicate that a reaction between O2- and NO is unlikely to account for their opposing effects on DNA synthesis.