CARBON-CENTERED FREE-RADICAL FORMATION DURING THE METABOLISM OF HYDRAZINE DERIVATIVES BY NEUTROPHILS

The neutrophil-catalyzed metabolism of hydrazine derivatives to carbon -centered radicals was investigated by the spin-trapping technique usi ng alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN). Oxidation of methylhydrazine (MeH), dimethylhydrazine (DMH), phenylethylhydrazine o r procarbazine by neutrophils from rat peritoneal exudates led to the formation of alkyl radicals. The monosubstituted hydrazine oxidation b y phorbol ester (PMA)- or Zymocel-activated neutrophils generated, on average, 2- to 4-fold more POBN-alkyl adducts than di-substituted hydr azines. Supernatant from sonicated neutrophils generated similar yield s of radicals. Azide, an inhibitor of myeloperoxidase, effectively red uced the neutrophil-catalyzed radical yield from the oxidation of MeH but not DMH. On the other hand, superoxide dismutase and catalase effe ctively inhibited radical formation in DMH metabolism by PMA-activated neutrophils, in contrast to MeH metabolism. Our results show that neu trophils are able to metabolize hydrazine derivatives, the pathway dep ending on the hydrazine substitution. Alkyl radical production during the oxidation of mono-substituted derivatives, such as MeH, was mediat ed mainly by myeloperoxidase, and that of di-substituted derivatives, such as DMH, was mediated mainly by active oxygen species.