Identification of C8-methylguanine in the hydrolysates of DNA from rats administered 1,2-dimethylhydrazine: Evidence for in vivo DNA alkylation by methyl radicals

L. E.S. Netto, N. V.S. RamaKrishna, C. Kolar, E. L. Cavalieri, E. G. Rogan, Terence A. Lawson, O. Augusto

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38 Scopus citations

Abstract

C8-Methylguanine was identified in the neutral hydrolysates of DNA isolated from the liver or colon tissue of rats administered 1,2-dimethylhydrazine. In all the samples examined, the biologically isolated adducts were characterized by co-elution with synthetic C8-methylguanine under different high pressure liquid chromatography conditions. The sample isolated from liver DNA was also identified by UV spectroscopy at different pH values and by mass spectrometry. The estimated yields of C8-methylguanine obtained in hydrolysates of DNA from the liver or colon tissue were comparable to those of O6-methylguanine. C8-Methylguanine was not detected when the spin trap α-(4-pyridyl-1-oxide)-N-tert-butylnitrone was administered together with 1,2-dimethylhydrazine. The spin trap also inhibited N7-methylguanine and O6-methylguanine yields, although to a lesser extent. These results constitute the first evidence that DNA alkylation by carbon-centered radicals can occur in vivo.

Original languageEnglish (US)
Pages (from-to)21524-21527
Number of pages4
JournalJournal of Biological Chemistry
Volume267
Issue number30
StatePublished - Oct 25 1992

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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