M. Gamberini et Lcc. Leite, PROLIFERATION OF MOUSE FIBROBLASTS INDUCED BY 1,2-DIMETHYLHYDRAZINE AUTOXIDATION - ROLE OF IRON AND FREE-RADICALS, Biochemical and biophysical research communications, 234(1), 1997, pp. 44-47
Activation of 1,2-dimethylhydrazine (DMH) by prolonged auto-oxidation
(24-h) induced proliferation of mouse fibroblasts at low hydrazine con
centrations (0.1-1.0 mM) as determined by [H-3-methyl]-thymidine uptak
e of confluent quiescent cells. Incubations were performed under condi
tions 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 chelator
s, o-phenanthroline and desferrioxamine, demonstrates that the inducti
on of the proliferative effect is dependent on simple iron complexes.
Proliferation was also inhibited by superoxide dismutase, catalase, an
d mannitol, implicating reactive oxygen species, although superoxide d
ismutase and catalase also inhibited alkyl radical formation, as deter
mined 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. (C) 1997 Academic Press.