Differential Oxidation of Deoxyribose in DNA by γ and α-Particle Radiation

Collins, Christiane; Zhou, Xinfeng; Wang, Rong; Barth, Marita C.; Jiang, Tao; Coderre, Jeffrey A.; Dedon, Peter C.

doi:10.1667/rr3344

Cited by 20 publications

(29 citation statements)

References 39 publications

(73 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Irradiation dose response studies in isolated DNA caused formation rates of 1.5,12 9.7 and 57 lesions per 10 6 nt per Gy, respectively, which amounts to a ratio of 1:6.5:38. In cells, the rates were reduced to 0.002,12 0.45 and 0.22 lesions per 10 6 nt per Gy, respectively, and a ratio of 1:22:110.…”

Section: Discussionmentioning

confidence: 94%

See 1 more Smart Citation

Quantification of the 2-Deoxyribonolactone and Nucleoside 5′-Aldehyde Products of 2-Deoxyribose Oxidation in DNA and Cells by Isotope-Dilution Gas Chromatography Mass Spectrometry: Differential Effects of γ-Radiation and Fe²⁺−EDTA

et al. 2010

Self Cite

View full text Add to dashboard Cite

The oxidation of 2-deoxyribose in DNA has emerged as a critical determinant of the cellular toxicity of oxidative damage to DNA, with oxidation of each carbon producing a unique spectrum of electrophilic products. We have developed and validated an isotope-dilution gas chromatography-coupled mass spectrometry (GC-MS) method for the rigorous quantification of two major 2-deoxyribose oxidation products: the 2-deoxyribonolactone abasic site of 1’-oxidation and the nucleoside 5’-aldehyde of 5’-oxidation chemistry. The method entails elimination of these products as 5-methylene-2(5H)-furanone (5MF) and furfural, respectively, followed by derivatization with pentafluorophenylhydrazine (PFPH), addition of isotopically labeled PFPH derivatives as internal standards, extraction of the derivatives, and quantification by GC-MS analysis. The precision and accuracy of the method were validated with oligodeoxynucleotides containing the 2-deoxyribonolactone and nucleoside 5’-aldehyde lesions. Further, the well defined 2-deoxyribose oxidation chemistry of the enediyne antibiotics, neocarzinostatin and calicheamicin γ1I, was exploited in control studies, with neocarzinostatin producing 10 2-deoxyribonolactone and 300 nucleoside 5’-aldehyde per 106 nt per µM in accord with its established minor 1’- and major 5’-oxidation chemistry. Calicheamicin unexpectedly caused 1’-oxidation at a low level of 10 2-deoxyribonolactone per 106 nt per µM in addition to the expected predominance of 5’-oxidation at 560 nucleoside 5’-aldehyde per 106 nt per µM. The two hydroxyl radical-mediated DNA oxidants, γ-radiation and Fe2+-EDTA, produced nucleoside 5’-aldehyde at a frequency of 57 per 106 nt per Gy (G-value 74 nmol/J) and 3.5 per 106 nt per µM, respectively, which amounted to 40% and 35%, respectively, of total 2-deoxyribose oxidation as measured by a plasmid nicking assay. However, γ-radiation and Fe2+-EDTA produced different proportions of 2-deoxyribonolactone at 7% and 24% of total 2-deoxyribose oxidation, respectively, with frequencies of 10 lesions per 106 nt per Gy (G-value, 13 nmol/J) and 2.4 lesions per 106 nt per µM. Studies in TK6 human lymphoblastoid cells, in which the analytical data were corrected for losses sustained during DNA isolation, revealed background levels of 2-deoxyribonolactone and nucleoside 5’-aldehyde of 9.7 and 73 lesions per 106 nt, respectively. γ-Irradiation of the cells caused increases of 0.045 and 0.22 lesions per 106 nt per Gy, respectively, which represents a ~250-fold quenching effect of the cellular environment similar to that observed in previous studies. The proportions of the various 2-deoxyribose oxidation products generated by γ-radiation are similar for purified DNA and cells. These results are consistent with solvent exposure as a major determinant of hydroxyl radical reactivity with 2-deoxyribose in DNA, but the large differences between γ-radiation and Fe2+-EDTA suggest that factors other than hydroxyl radical reactivity govern DNA oxidation chemistry.

show abstract

Section: Discussionmentioning

confidence: 94%

“…Cultures of TK6 human lymphoblastoid cells, grown to 1 × 10 6 cells per mL as described previously,12 were washed three times with PBS and resuspended in PBS at a concentration of 5 × 10 6 cells per mL. The suspensions (10 mL) were exposed to γ-radiation (0–500 Gy), at ambient temperature at a dose-rate of 161.3 Gy/min.…”

Section: Experimental Methodsmentioning

confidence: 99%

Quantification of the 2-Deoxyribonolactone and Nucleoside 5′-Aldehyde Products of 2-Deoxyribose Oxidation in DNA and Cells by Isotope-Dilution Gas Chromatography Mass Spectrometry: Differential Effects of γ-Radiation and Fe²⁺−EDTA

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…The presently reported work highlights the putative role of sugar alterations in the indirect biological effects of ionizing radiation and the treatment with radiomimetic drugs. It is now admitted that several diffusible electrophiles are produced by radical oxidation of 2-deoxyribose (38). The sugar derivatives bearing reactive aldehydes, such as butenedialdehyde and 2 are able to form, in the vicinity of strand breaks, stable DNA adducts, the reactions being favored by the secondary structure of DNA.…”

Section: Discussionmentioning

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.

147

161

View full text Add to dashboard Cite

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

show abstract

“…Ionizing radiation (IR) can generate breaks primarily via the generation of reactive oxygen species such as hydroxyl radicals (Bresler et al, 1979;Ward, 1988;Swarts et al, 2007). The reactive oxygen by-products of aerobic metabolism can similarly give rise to strand breaks (Mikkelsen and Wardman, 2003;Collins et al, 2005). UV irradiation causes base pair lesions that can lead to transient strand breakage during nucleotide excision repair (Sinha and Hader, 2002).…”

Section: Introductionmentioning

confidence: 99%

Escherichia coli radD (yejH) gene: a novel function involved in radiation resistance and double‐strand break repair

Chen

Byrne

Wood

et al. 2015

Molecular Microbiology

View full text Add to dashboard Cite

Summary A transposon insertion screen implicated the yejH gene in the repair of ionizing radiation-induced damage. The yejH gene, which exhibits significant homology to the human transcription-coupled DNA repair gene XPB, is involved in the repair of double strand DNA breaks. Deletion of yejH significantly sensitized cells to agents that cause double strand breaks (ionizing radiation, UV radiation, ciprofloxacin). In addition, deletion of both yejH and radA hypersensitized the cells to ionizing radiation, UV, and ciprofloxacin damage, indicating that these two genes have complementary repair functions. The ΔyejH ΔradA double deletion also showed a substantial decline in viability following an induced double-strand DNA break, of a magnitude comparable to the defect measured when the recA, recB, recG, or priA genes are deleted. The ATPase activity and C-terminal zinc finger motif of yejH play an important role in its repair function, as targeted mutant alleles of yejH did not rescue sensitivity. We propose that yejH be re-named radD, reflecting its role in the DNA repair of radiation damage.

show abstract

Differential Oxidation of Deoxyribose in DNA by γ and α-Particle Radiation

Cited by 20 publications

References 39 publications

Quantification of the 2-Deoxyribonolactone and Nucleoside 5′-Aldehyde Products of 2-Deoxyribose Oxidation in DNA and Cells by Isotope-Dilution Gas Chromatography Mass Spectrometry: Differential Effects of γ-Radiation and Fe²⁺−EDTA

Quantification of the 2-Deoxyribonolactone and Nucleoside 5′-Aldehyde Products of 2-Deoxyribose Oxidation in DNA and Cells by Isotope-Dilution Gas Chromatography Mass Spectrometry: Differential Effects of γ-Radiation and Fe²⁺−EDTA

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

Escherichia coli radD (yejH) gene: a novel function involved in radiation resistance and double‐strand break repair

Contact Info

Product

Resources

About

Differential Oxidation of Deoxyribose in DNA by γ and α-Particle Radiation

Cited by 20 publications

References 39 publications

Quantification of the 2-Deoxyribonolactone and Nucleoside 5′-Aldehyde Products of 2-Deoxyribose Oxidation in DNA and Cells by Isotope-Dilution Gas Chromatography Mass Spectrometry: Differential Effects of γ-Radiation and Fe2+−EDTA

Quantification of the 2-Deoxyribonolactone and Nucleoside 5′-Aldehyde Products of 2-Deoxyribose Oxidation in DNA and Cells by Isotope-Dilution Gas Chromatography Mass Spectrometry: Differential Effects of γ-Radiation and Fe2+−EDTA

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

Escherichia coli radD (yejH) gene: a novel function involved in radiation resistance and double‐strand break repair

Contact Info

Product

Resources

About

Quantification of the 2-Deoxyribonolactone and Nucleoside 5′-Aldehyde Products of 2-Deoxyribose Oxidation in DNA and Cells by Isotope-Dilution Gas Chromatography Mass Spectrometry: Differential Effects of γ-Radiation and Fe²⁺−EDTA

Quantification of the 2-Deoxyribonolactone and Nucleoside 5′-Aldehyde Products of 2-Deoxyribose Oxidation in DNA and Cells by Isotope-Dilution Gas Chromatography Mass Spectrometry: Differential Effects of γ-Radiation and Fe²⁺−EDTA