Tandem Lesions and Other Products in X-Irradiated DNA Oligomers

Box, Harold C.; Budzinski, Edwin E.; Dawidzik, Jean B.; Wallace, John C.; Iijima, Herbert

doi:10.2307/3579782

Cited by 85 publications

(69 citation statements)

References 6 publications

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“…For instance, a G^T intrastrand crosslink lesion, where the C8 of guanine is covalently bonded to the methyl carbon of its neighboring thymine, was shown to be induced in calf thymus DNA upon γ irradiation (13). These previous studies also revealed that the intrastrand crosslink lesions are initiated from a single pyrimidine radical (9)(10)(11)13,(15)(16)(17). In this regard, hydroxyl radical ( · OH) can either be added to the C5 and C6 carbon atoms of cytosine, thymine and 5-methylcytosine, or abstract a hydrogen atom from the 5-methyl group of the latter two pyrimidine bases (21).…”

Section: Introductionmentioning

confidence: 70%

“…The secondary radical of thymine can then couple with the C8 of the vicinal 5′ guanine to give rise to the G^T crosslink (8,10,12,13). Given that · OH can also result in the formation of single-base lesions, it is important for us to quantify both the single-base and the intrastrand crosslink lesions.…”

Section: Lc-ms/ms Identification and Quantification Of Dna Lesions Inmentioning

confidence: 99%

“…Previous work by Box, Cadet, Wang and their coworkers (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) uncovered that γ-or X-ray irradiation of aqueous solutions of DNA components can induce the formation of several intrastrand crosslink lesions. For instance, a G^T intrastrand crosslink lesion, where the C8 of guanine is covalently bonded to the methyl carbon of its neighboring thymine, was shown to be induced in calf thymus DNA upon γ irradiation (13).…”

Section: Introductionmentioning

confidence: 99%

“…In this regard, hydroxyl radical ( · OH) can either be added to the C5 and C6 carbon atoms of cytosine, thymine and 5-methylcytosine, or abstract a hydrogen atom from the 5-methyl group of the latter two pyrimidine bases (21). Both processes lead to the formation of pyrimidine base-centered secondary radicals, which may attack their neighboring purine bases to yield intrastrand crosslink lesions (9)(10)(11)13,(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

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Identification and Quantification of a Guanine−Thymine Intrastrand Cross-Link Lesion Induced by Cu(II)/H₂O₂/Ascorbate

Hong

Cao

Wang

et al. 2006

Chem. Res. Toxicol.

136

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Reactive oxygen species (ROS) can be induced by both endogenous and exogenous processes and they can damage biological molecules including nucleic acids. It was shown that X-or γ-ray irradiation of aqueous solutions of DNA, during which · OH is one of the major ROS, can lead to the formation of intrastrand crosslink lesions where the neighboring nucleobases in the same DNA strand are covalently bonded. Previous 32 P-postlabeling studies suggested that the intrastrand crosslink lesions may arise from Fenton reaction, which also induces the formation of · OH; the structures of the proposed intrastrand crosslink lesions, however, have not been determined. Here we showed for the first time that the treatment of calf thymus DNA with Cu(II)/H 2 O 2 /ascorbate could lead to the formation of an intrastrand crosslink lesion, i.e., G^T, where the C8 of guanine is covalently bonded to the neighboring 3′ thymine through its methyl carbon. LC-MS/MS quantification results showed dose-responsive formation of G^T. In addition, the yield of the intrastrand crosslink was approximately three orders of magnitude lower than those of commonly observed single-base lesions, that is, 8-oxo-7,8-dihydro-2′-deoxyguanosine, 5-(hydroxymethyl)-2′-deoxyuridine and 5-formyl-2′-deoxyuridine. The induction of intrastrand crosslink lesion in calf thymus DNA by Fenton reagents in vitro suggests that this type of lesion might be formed endogenously in mammalian cells.

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Section: Introductionmentioning

confidence: 70%

Section: Lc-ms/ms Identification and Quantification Of Dna Lesions Inmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identification and Quantification of a Guanine−Thymine Intrastrand Cross-Link Lesion Induced by Cu(II)/H₂O₂/Ascorbate

Hong

Cao

Wang

et al. 2006

Chem. Res. Toxicol.

136

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“…Recent works have demonstrated that in dinucleoside monophosphates (11,12) and in oligonucleotides (11,13) peroxyl radicals of pyrimidine bases could efficiently react with a vicinal DNA base. Indeed, it has been recently reported that in DNA addition of pyrimidine peroxyl radicals onto the C8 of a purine base is capable of producing 8-oxodGuo involved in tandem lesions neighboring a formylamine (dF) residue (14,15).…”

mentioning

confidence: 99%

HO ^• radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases

Bergeron

Auvré

Radicella

et al. 2010

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

123

113

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Reaction of HO• radicals with double-stranded calf thymus DNA produces high levels of and, to a minor extent, . Formation of the hydroxylated purine lesions is explained by addition of HO • to the C8 position of the purine moiety. It has been reported that tandem lesions containing a formylamine residue neighboring 8-oxodGuo could be produced through addition of a transiently generated pyrimidine peroxyl radical onto the C8 of an adjacent purine base. Formation of such tandem lesions accounted for ≈10% of the total 8-oxodGuo. In the present work we show that addition of HO • onto the C8 of purine accounts for only ∼5% of the generated 8-oxodGuo. About 50% of the 8-hydroxylated purine lesions, including 8-oxodGuo and 8-oxodAdo, are involved in tandem damage and are produced by peroxyl addition onto the C8 of a vicinal purine base. In addition, the remaining 45% of the 8-oxodGuo are produced by an electron transfer reaction, providing an explanation for the higher yield of formation of 8-oxodGuo compared to 8-oxodAdo. Interestingly, we show that >40% of the 8-oxodGuo involved in tandem lesions is refractory to excision by DNA glycosylases. Altogether our results demonstrate that, subsequently to a single oxidation event, peroxidation reactions significantly increase the yield of formation of hydroxylated purine modifications, generating a high proportion of tandem lesions partly refractory to base excision repair.DNA damage | DNA repair | peroxidation reaction | tandem lesions F ormation of oxidatively generated DNA lesions is associated with the occurrence of degenerative diseases, cancer, and aging (1). Therefore, reactions of reactive oxygen species, and among them the highly genotoxic hydroxyl radical (HO • ), with DNA constituents have been extensively studied during the last three decades (2). 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) and, to a minor extent the corresponding adenine derivative 8-oxo-7,8-dihydro-2′-deoxyadenosine (8-oxodAdo), have been shown to be significantly generated in cellular DNA under various conditions of oxidative stress. More than 20 years ago (3) it was established that in the presence of HO• (produced either by the indirect effect of ionizing radiation or by Fenton-type reactions) the mechanism of formation of 8-hydroxylated purine lesions (8-oxoPur), including both 8-oxodGuo and 8-oxodAdo, involves addition of HO• to the C8 position of the purine bases, followed by an oxidation reaction (for a review see refs. 2 and 4). In addition, 8-oxoPur could be also produced by a one-electron oxidation process followed by hydration of the purine radical cation thus generated, producing following oxidation mainly 8-oxodGuo due to efficient charge transfer processes (5, 6) combined with the relatively low ionization potential of guanine compared to other DNA constituents.In addition, the pioneering work of Box and coworkers (7-10) suggested the possible formation of tandem lesions, constituted of two adjacent modifications. Recent works have demonstrated that in dinucleoside monophosp...

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The Chemical Reactions of DNA Damage and Degradation

Gates

2006

Reviews of Reactive Intermediate Chemistry

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Tandem Lesions and Other Products in X-Irradiated DNA Oligomers

Cited by 85 publications

References 6 publications

Identification and Quantification of a Guanine−Thymine Intrastrand Cross-Link Lesion Induced by Cu(II)/H₂O₂/Ascorbate

Identification and Quantification of a Guanine−Thymine Intrastrand Cross-Link Lesion Induced by Cu(II)/H₂O₂/Ascorbate

HO ^• radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases

The Chemical Reactions of DNA Damage and Degradation

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Tandem Lesions and Other Products in X-Irradiated DNA Oligomers

Cited by 85 publications

References 6 publications

Identification and Quantification of a Guanine−Thymine Intrastrand Cross-Link Lesion Induced by Cu(II)/H2O2/Ascorbate

Identification and Quantification of a Guanine−Thymine Intrastrand Cross-Link Lesion Induced by Cu(II)/H2O2/Ascorbate

HO • radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases

The Chemical Reactions of DNA Damage and Degradation

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Identification and Quantification of a Guanine−Thymine Intrastrand Cross-Link Lesion Induced by Cu(II)/H₂O₂/Ascorbate

Identification and Quantification of a Guanine−Thymine Intrastrand Cross-Link Lesion Induced by Cu(II)/H₂O₂/Ascorbate

HO ^• radicals induce an unexpected high proportion of tandem base lesions refractory to repair by DNA glycosylases