Formation of 8-methylguanine as a result of DNA alkylation by methyl radicals generated during horseradish peroxidase-catalyzed oxidation of methylhydrazine

Ohara Augusto, Ercole Cavalieri, Eleanor G Rogan, N. V S RamaKrishna, Carol Kolar

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Abstract

Methylhydrazine oxidation promoted by horseradish peroxidase-H2O2 or ferricyanide led to the generation of high yields of methyl radicals and to the formation of 7-methylguanine and 8-methylguanine upon interaction with calf thymus DNA. Methyl radicals were identified by spin-trapping experiments with α-(4-pyridyl-1-oxide)-N-tert-butyl nitrone and tert-nitrosobutane. The methylated guanine products were identified in the neutral hydrolysates of treated DNA by high pressure liquid chromatography (HPLC) analysis and spiking with authentic samples. The structure of 8-methylguanine, a product not previously reported in enzymatic systems, was confirmed by HPLC, UV absorbance, and mass spectrometry. The formation of 8-methylguanine suggests a possible role for carbon-centered radicals as DNA-alkylating agents.

Original languageEnglish (US)
Pages (from-to)22093-22096
Number of pages4
JournalJournal of Biological Chemistry
Volume265
Issue number36
Publication statusPublished - Dec 1 1990

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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