Oxidative DNA damage by a metabolite of carcinogenic and reproductive toxic nitrobenzene in the presence of NADH and Cu(II).

Abstract:

:The mechanism of DNA damage induced by metabolites of nitrobenzene was investigated in relation to the carcinogenicity and reproductive toxicity of nitrobenzene. Nitrosobenzene, a nitrobenzene metabolite, induced NADH plus Cu(II)-mediated DNA cleavage frequently at thymine and cytosine residues. Catalase and bathocuproine inhibited the DNA damage, suggesting the involvement of H2O2 and Cu(I). Typical free hydroxyl radical scavengers showed no inhibitory effects on DNA damage. Nitrosobenzene caused the formation of 8-oxo-7, 8-dihydro-2'-deoxyguanosine in calf thymus DNA in the presence of NADH and Cu(II). ESR spectroscopic study has confirmed that nitrosobenzene is reduced by NADH to the phenylhydronitroxide radical even in the absence of Cu(II). These results suggest that nitrosobenzene can be reduced non-enzymatically by NADH, and the redox cycle reaction resulted in oxidative DNA damage due to the copper-oxygen complex, derived from the reaction of Cu(I) with H2O2.

authors

Ohkuma Y,Kawanishi S

doi

10.1006/bbrc.1999.0525

subject

Has Abstract

pub_date

1999-04-13 00:00:00

pages

555-60

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(99)90525-9

journal_volume

257

pub_type

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