Proliferation of mouse fibroblasts induced by 1,2-dimethylhydrazine auto-oxidation: role of iron and free radicals.

Activation of 1,2-dimethylhydrazine (DMH) by prolonged auto-oxidation (24-h) induced proliferation of mouse fibroblasts at low hydrazine concentrations (0.1-1.0 mM) as determined by [3H-methyl]-thymidine uptake of confluent quiescent cells. Incubations were performed under conditions in which alkyl radicals are slowly formed by DMH auto-oxidation. The proliferative stimulus induced by DMH auto-oxidation complements that induced by insulin, PMA, and EGF. Inhibition by the iron chelators, o-phenanthroline and desferrioxamine, demonstrates that the induction of the proliferative effect is dependent on simple iron complexes. Proliferation was also inhibited by superoxide dismutase, catalase, and mannitol, implicating reactive oxygen species, although superoxide dismutase and catalase also inhibited alkyl radical formation, as determined by spin-trapping. These results suggest that cell proliferation induced by DMH auto-oxidation is mediated by reactive oxygen species, mainly the hydroxyl radical, and is dependent on simple iron complexes, possibly involving the Fenton reaction.