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.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Ohkuma Y,Kawanishi Sdoi
10.1006/bbrc.1999.0525subject
Has Abstractpub_date
1999-04-13 00:00:00pages
555-60issue
2eissn
0006-291Xissn
1090-2104pii
S0006-291X(99)90525-9journal_volume
257pub_type
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