Abstract
| - Many arylhydrazines are genotoxins, although the mechanism oftheir genotoxicity isunknown. Previous studies have shown that arylhydrazines aremetabolized to arenediazoniumions, which produce C8-arylguanine adducts in DNA suggesting theintermediacy of an arylradical. Here we have looked for the formation of aryl radicalsfrom arylhydrazines andmicrosomes by ESR spin trapping. Only hydroxyl radicals aretrapped upon incubation ofp-methylphenylhydrazine with rat liver microsomes and5,5-dimethyl-1-pyrroline N-oxide(DMPO). However, hydroxyl and aryl radicals were trapped uponincubation of p-(methoxymethyl)phenylhydrazine with rat liver microsomes. Evidence forhydroperoxyl radical formation was also obtained. In contrast, when either of thesesubstrates was incubated withmicrosomes from C5O cells, aryl and hydroxyl radicals were trapped.The ESR signal intensityof the spin-trapped aryl radicals parallels the extent ofC8-arylguanine formation in DNA,and therefore, the aryl radical is likely the intermediate responsiblefor C8-arylguanine adductformation. Aryl radicals and C8-arylguanine adducts may be relatedto the genotoxicity ofarylhydrazines and related compounds that are oxidatively metabolizedto arenediazoniumions, the precursor to aryl radicals, including arylalkyl nitrosamines,arylazo compounds, andtriazenes.
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