Measurement of the Main Photooxidation Products of 2′-Deoxyguanosine Using Chromatographic Methods Coupled to Mass Spectrometry

Ravanat, Jean‐Luc; Remaud, Gaëlle; Cadet, Jean

doi:10.1006/abbi.1999.1610

Cited by 55 publications

(42 citation statements)

References 24 publications

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“…The fluorescence detector was calibrated externally using the samples prepared by the derivatization of known quantities of the authentic guanidine hydrochloride; the amounts of oxazolone in the irradiated oligonucleotides were calculated from these calibration curves. The accuracy of this method for the quantitation of the Z lesions was confirmed by an HPLC-MS/MS assay (21).…”

Section: Methodsmentioning

confidence: 93%

“…The latter lesions were converted to the more stable Z lesions by storage of the irradiated samples in the dark at room temperature for ϳ48 h (18) and were detected by a post-fluorescence HPLC method (20). The accuracy of this method for the quantitation of the Z lesions in DNA was confirmed by the HPLC-MS/MS assay (21). The depletion of guanine and formation of 8-oxoGua lesions was assayed by reversed-phase HPLC methods after enzymatic digestion of the irradiated samples.…”

Section: Dynamics Of Guanine Lesion Formation-the Combination Of the mentioning

confidence: 99%

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Oxidative DNA Damage Associated with Combination of Guanine and Superoxide Radicals and Repair Mechanisms via Radical Trapping

Misiaszek

Crean

Joffe

et al. 2004

Journal of Biological Chemistry

209

250

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Section: Methodsmentioning

confidence: 93%

Section: Dynamics Of Guanine Lesion Formation-the Combination Of the mentioning

confidence: 99%

Oxidative DNA Damage Associated with Combination of Guanine and Superoxide Radicals and Repair Mechanisms via Radical Trapping

Misiaszek

Crean

Joffe

et al. 2004

Journal of Biological Chemistry

209

250

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“…Collected fractions containing 4 were dissolved in water, and a UV absorption spectrum was recorded by using a Hewlett-Packard (Les Ullis, France) model 8453 apparatus. The molecular absorption coefficient, which is identical for at least isomers 4c and 4d, was determined by using 1 H NMR as described (42) …”

Section: Methodsmentioning

confidence: 99%

Oxidation of the sugar moiety of DNA by ionizing radiation or bleomycin could induce the formation of a cluster DNA lesion

Regulus¹,

Duroux²,

Bayle

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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147

161

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Bleomycin, a radiomimetic drug currently used in human cancer therapy, is a well known carcinogen. Its toxicity is mostly attributed to its potentiality to induce DNA double strand breaks likely arising from the formation of two vicinal DNA strand breaks, initiated by C4-hydrogen abstraction on the 2-deoxyribose moiety.In this work we demonstrate that such a hydrogen abstraction reaction is able to induce the formation of a clustered DNA lesion, involving a 3 strand break together with a modified sugar residue exhibiting a reactive ␣,␤-unsaturated aldehyde that further reacts with a proximate cytosine base. The lesion thus produced was detected as a mixture of four isomers by HPLC coupled to tandem mass spectrometry subsequent to DNA extraction and enzymatic digestion. The modified nucleosides that constitute new types of cytosine adducts were identified as the likely two pairs of diastereomers of 6-(2-deoxy-␤-Derythro-pentofuranosyl)-2-hydroxy-3(3-hydroxy-2-oxopropyl)-2,6-dihydroimidazo[1,2-c]-pyrimidin-5(3H)-one as inferred from mass spectrometry and NMR analyses of the chemically synthesized nucleosides. We demonstrate that bleomycin, and to a minor extent ionizing radiation, are able to induce significant amounts of the cytosine damage in cellular DNA. In addition, the repair kinetic of the lesion in a human lymphocyte cell line is rather slow, with a half-life of 10 h. The 2 -deoxycytidine adducts thus characterized that represent the first example of complex DNA lesions isolated and identified in cellular DNA upon one radical hit are likely to play an important role in the toxicity of bleomycin.cluster lesions ͉ DNA damage ͉ DNA repair

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“…The total eluent was directed to the turbo ion spray source. Chlorinated nucleosides were detected using electrospray ionization tandem mass spectrometry in the multiple reaction monitoring mode (22,23). Specific transitions used to detect chlorinated nucleosides in the positive ionization mode were those between the molecular cation of the chlorinated nucleosides and the characteristic chlorinated daughter ion formed from the loss of the sugar moiety: 8-Cl-Guo, m/z 318 3 186; 8-Cl-dGuo, m/z 302 3 186; 8-Cl-Ado, m/z 302 3 170; 8-Cl-dAdo, m/z 286 3 170; 5-Cl-Cyd, m/z 278 3 146, and 5-Cl-dCyd, m/z 262 3 146.…”

Section: Methodsmentioning

confidence: 99%

Chlorination of Guanosine and Other Nucleosides by Hypochlorous Acid and Myeloperoxidase of Activated Human Neutrophils

Masuda¹,

Suzuki²,

Friesen³

et al. 2001

Journal of Biological Chemistry

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133

119

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Activated human neutrophils secrete myeloperoxidase, which generates HOCl from H 2 O 2 and Cl ؊ . We have found that various (2-deoxy)nucleosides react with HOCl to form chlorinated (2-deoxy)nucleosides, including novel 8-chloro(2-deoxy)guanosine, 5-chloro(2-deoxy)cytidine, and 8-chloro(2-deoxy)adenosine formed in yields of 1.6, 1.6, and 0.2%, respectively, when 0.5 mM nucleoside reacted with 0.5 mM HOCl at pH 7.4. The relative chlorination, oxidation, and nitration activities of HOCl, myeloperoxidase, and activated human neutrophils in the presence and absence of nitrite were studied by analyzing 8-chloro-, 8-oxo-7,8-dihydro-, and 8-nitroguanosine, respectively, using guanosine as a probe. 8-Chloroguanosine was always more easily formed than 8-oxo-7,8-dihydro-or 8-nitro-guanosine. Using electrospray ionization tandem mass spectrometry, we show that several chlorinated nucleosides including 8-chloro(2-deoxy)guanosine are formed following exposure of isolated DNA or RNA to HOCl. Micromolar concentrations of tertiary amines such as nicotine and trimethylamine dramatically enhanced chlorination of free (2-deoxy)nucleosides and nucleosides in RNA by HOCl. As the G؊463A polymorphism of the MPO gene, which strongly reduces myeloproxidase mRNA expression, is associated with a reduced risk of lung cancer, chlorination damage of DNA /RNA and nucleosides by myeloperoxidase and its enhancement by nicotine may be important in the pathophysiology of human diseases associated with tobacco habits.

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Measurement of the Main Photooxidation Products of 2′-Deoxyguanosine Using Chromatographic Methods Coupled to Mass Spectrometry

Cited by 55 publications

References 24 publications

Oxidative DNA Damage Associated with Combination of Guanine and Superoxide Radicals and Repair Mechanisms via Radical Trapping

Oxidative DNA Damage Associated with Combination of Guanine and Superoxide Radicals and Repair Mechanisms via Radical Trapping

Oxidation of the sugar moiety of DNA by ionizing radiation or bleomycin could induce the formation of a cluster DNA lesion

Chlorination of Guanosine and Other Nucleosides by Hypochlorous Acid and Myeloperoxidase of Activated Human Neutrophils

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