Generation of guanine-thymine cross-links in human cells by one-electron oxidation mechanisms

Guru S. Madugundu, J. Richard Wagner, Jean Cadet, Konstantin Kropachev, Byeong Hwa Yun, Nicholas E. Geacintov, Vladimir Shafirovich

Research output: Contribution to journalArticle

Abstract

The one-electron oxidation of cellular DNA in cultured human HeLa cells initiated by intense nanosecond 266 nm laser pulse irradiation produces cross-links between guanine and thymine bases (G*-T*), characterized by a covalent bond between C8 guanine (G*) and N3 thymine (T*) atoms. The DNA lesions were quantified by isotope dilution LC-MS/MS methods in the multiple reaction-monitoring mode using isotopically labeled [ 15N, 13C]-nucleotides as internal standards. Among several known pyrimidine and 8-oxo-7,8-dihydroguanine lesions, the G*-T* cross-linked lesions were detected at levels of ∼0.21 and 1.19 d(G*-T*) lesions per 106 DNA bases at laser intensities of 50 and 280 mJ/cm2/pulse, respectively.

Original languageEnglish (US)
Pages (from-to)1031-1033
Number of pages3
JournalChemical research in toxicology
Volume26
Issue number7
DOIs
StatePublished - Jul 15 2013

ASJC Scopus subject areas

  • Toxicology

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    Madugundu, G. S., Wagner, J. R., Cadet, J., Kropachev, K., Yun, B. H., Geacintov, N. E., & Shafirovich, V. (2013). Generation of guanine-thymine cross-links in human cells by one-electron oxidation mechanisms. Chemical research in toxicology, 26(7), 1031-1033. https://doi.org/10.1021/tx400158g