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


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 [(15)N, (13)C]-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 10(6) DNA bases at laser intensities of 50 and 280 mJ/cm(2)/pulse, respectively.

SUBMITTER: Madugundu GS 

PROVIDER: S-EPMC3812307 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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

Madugundu Guru S GS   Wagner J Richard JR   Cadet Jean J   Kropachev Konstantin K   Yun Byeong Hwa BH   Geacintov Nicholas E NE   Shafirovich Vladimir V  

Chemical research in toxicology 20130611 7


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 [(15)N, (13)C]-nucleotides as internal standards. Among several known pyrimidine  ...[more]

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