Aryl radical formation during the metabolism of arylhydrazines by microsomes

Chemical Research in Toxicology
P M GannettB Toth

Abstract

Many arylhydrazines are genotoxins, although the mechanism of their genotoxicity is unknown. Previous studies have shown that arylhydrazines are metabolized to arenediazonium ions, which produce C8-arylguanine adducts in DNA suggesting the intermediacy of an aryl radical. Here we have looked for the formation of aryl radicals from arylhydrazines and microsomes by ESR spin trapping. Only hydroxyl radicals are trapped upon incubation of p-methylphenylhydrazine with rat liver microsomes and 5,5-dimethyl-1-pyrroline N-oxide (DMPO). However, hydroxyl and aryl radicals were trapped upon incubation of p-(methoxymethyl)phenylhydrazine with rat liver microsomes. Evidence for hydroperoxyl radical formation was also obtained. In contrast, when either of these substrates was incubated with microsomes from C5O cells, aryl and hydroxyl radicals were trapped. The ESR signal intensity of the spin-trapped aryl radicals parallels the extent of C8-arylguanine formation in DNA, and therefore, the aryl radical is likely the intermediate responsible for C8-arylguanine adduct formation. Aryl radicals and C8-arylguanine adducts may be related to the genotoxicity of arylhydrazines and related compounds that are oxidatively metabolized to arenediazonium...Continue Reading

Citations

Mar 26, 2003·Journal of Chromatography. a·Carlos Bravo-Díaz, Elisa González-Romero
Oct 6, 2000·Free Radical Biology & Medicine·B QuinteroM C Cabeza
Dec 7, 2007·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Kazunari KondoTamio Maitani
Mar 14, 2018·Organic & Biomolecular Chemistry·V Vongsutilers, P M Gannett
Aug 3, 2005·Journal of Biomolecular Structure & Dynamics·Sue Heavner, Peter M Gannett
Aug 16, 2003·The Journal of Organic Chemistry·Elizabeth C WesternKevin H Shaughnessy

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