Damage to Isolated DNA Mediated by Singlet Oxygen

Ravanat, Jean‐Luc; Saint-Pierre, Christine; Mascio, Paolo Di; Martinez, Gláucia Regina; Medeiros, Marisa Helena Gennari de; Cadet, Jean

doi:10.1002/1522-2675(20011219)84:12<3702::aid-hlca3702>3.0.co;2-y

Cited by 96 publications

(64 citation statements)

References 31 publications

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“…Sodium azide, a known hydroxyl and 1 O 2 scavenger (40) abolished 8-oxo-dGuo formation (p < 0.0001 -< 0.002). The ability of this scavenger to be effective when other hydroxyl radical scavengers failed suggests that 1 O 2 is the reactive oxygen species responsible for 8-oxo-dGuo formation as suggested by Cadet (39). In this mechanism 8-oxo-dGuo is derived from an unstable 4,8-endoperoxide intermediate.…”

Section: Discussionmentioning

confidence: 97%

“…The same mutational pattern (G to T transversions, 63.0 % of 65 base substitutions) was obtained after transfection of 1 O 2 -treated M13lacZ bacteriophage DNA in Escherichia coli (49). Also, 8-oxo-dGuo is a frequent lesion detected in DNA exposed to 1 O 2 (39,(50)(51)(52). These findings suggest that 1 O 2 causes 8-oxo-dGuo formation and this accounts for the G to T transversions.…”

Section: Discussionmentioning

confidence: 99%

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Formation of 8-Oxo-7,8-dihydro-2‘-deoxyguanosine (8-Oxo-dGuo) by PAH o-Quinones: Involvement of Reactive Oxygen Species and Copper(II)/Copper(I) Redox Cycling

Park

Gopishetty

Szewczuk

et al. 2005

Chem. Res. Toxicol.

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Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants and procarcinogens that require activation by host metabolism. Metabolic activation of PAHs by AldoKeto-Reductases (AKRs) leads to formation of reactive and redox active o-quinones, which may cause oxidatively generated DNA damage. Spectrophotometric assays showed that NADPH caused PAH o-quinones to enter futile redox-cycles, which result in the depletion of excess cofactor. Copper (II) amplified NADPH-dependent redox-cycling of the o-quinones. Concurrent with NADPH oxidation, molecular oxygen was consumed, indicating the production of ROS. To determine whether PAH o-quinones can cause 8-oxo-dGuo formation in salmon testis DNA, three pre-requisite experimental conditions were satisfied. Quantitative complete enzymatic hydrolysis of DNA was achieved, adventitious oxidation of dGuo was eliminated by the use of chelex and desferal, and basal levels of less than 2.0 8-oxo-dGuo/10 5 dGuo were obtained. The HPLC-ECD analytical method was validated by spiking the DNA with standard 8-oxo-dGuo and demonstrating quantitative recovery. HPLC-ECD analysis revealed that in the presence of NADPH and Cu(II), submicromolar concentrations of PAH o-quinones generated > 60.0 8-oxo-dGuo adducts/10 5 dGuo. The rank order of 8-oxo-dGuo generated in isolated DNA was NP-1,2-dione > BA-3,4-dione > 7,12-DMBA-3,4-dione > BP-7,8-dione. The formation of 8-oxo-dGuo by PAH o-quinones was concentrationdependent. It was completely or partially inhibited when catalase, tiron or a Cu(I) specific chelator, bathocuproine were added, indicating the requirement for H 2 O 2 , O 2 − and Cu(I), respectively. Methional which is a copper-hydroperoxo complex (Cu(I)OOH) scavenger also suppressed 8-oxodGuo formation. By contrast, mannitol, sodium benzoate and sodium formate, which act as hydroxyl radical scavengers, did not block its formation. Sodium azide which can act as both a hydroxyl radical and 1 O 2 scavenger abolished the formation of 8-oxo-dGuo. These data showed that the production of 8-oxo-dGuo was dependent on Cu(II) /Cu(I) catalyzed redox cycling of PAH o-quinones to

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Formation of 8-Oxo-7,8-dihydro-2‘-deoxyguanosine (8-Oxo-dGuo) by PAH o-Quinones: Involvement of Reactive Oxygen Species and Copper(II)/Copper(I) Redox Cycling

Park

Gopishetty

Szewczuk

et al. 2005

Chem. Res. Toxicol.

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“…This excited species, which can be generated by an energy transfer mechanism (6,7), exhibits high reactivity and can be produced in biological systems (8,9). In mammalian cells, O 2 ( 1 ⌬ g ) can be generated during oxidative stress, and it is able to attack DNA, protein thiol groups, and membrane lipids (11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”

mentioning

confidence: 99%

Changes in the Spin State and Reactivity of Cytochrome c Induced by Photochemically Generated Singlet Oxygen and Free Radicals

Estevam

Nascimento

Baptista

et al. 2004

Journal of Biological Chemistry

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This work compares the effect of photogenerated singlet oxygen (O 2 ( 1 ⌬ g )) (type II mechanism) and free radicals (type I mechanism) on cytochrome c structure and reactivity. Both reactive species were obtained by photoexcitation of methylene blue (MB ؉ ) in the monomer and dimer forms, respectively. The monomer form is predominant at low dye concentrations (up to 8 M) or in the presence of an excess of SDS micelles, while dimers are predominant at 0.7 mM SDS. Over a pH range in which cytochrome c is in the native form, O 2 ( 1 ⌬ g ) and free radicals induced a Soret band blue shift (from 409 to 405 nm), predominantly. EPR measurements revealed that the blue shift of the Soret band was compatible with conversion of the heme iron from its native low spin state to a high spin state with axial symmetry (g ϳ 6.0). Soret band bleaching, due to direct attack on the heme group, was only detected under conditions that favored free radical production (MB ؉ dimer in SDS micelles) or in the presence of a less structured form of the protein (above pH 9.3). Matrix-assisted laser desorption ionization time-of-flight mass spectrometry of the heme group and the polypeptide chain of cytochrome c with Soret band at 405 nm (cytc405) revealed no alterations in the mass of the cytc405 heme group but oxidative modifications on methionine (Met 65 and Met 80 ) and tyrosine (Tyr 74 ) residues. Damage of cytc405 tyrosine residue impaired its reduction by diphenylacetaldehyde, but not by ␤-mercaptoethanol, which was able to reduce cytc405, generating cytochrome c Fe(II) in the high spin state (spin 2).

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“…Justification for this derives from: (i) ROS generated by UVA is predominantly 1 O 2 (85 %), rather than OH (15%) [14]; (ii) existing work on Aza/6-TG and UVA report 1 O 2 to be the major damaging species [35], presumably over and above that seen with UVA alone; plus (iii) guanine is sole the target for 1 O 2 under neutral aqueous conditions [38]; and (iv) 8-oxodG is the predominant form of DNA damage induced by 1 O 2 [39].…”

Section: Discussionmentioning

confidence: 99%

Combination of azathioprine and UVA irradiation is a major source of cellular 8-oxo-7,8-dihydro-2′-deoxyguanosine

Cooke¹,

Duarte²,

Cooper³

et al. 2008

DNA Repair

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Thiopurine antimetabolites, such as azathioprine (Aza) and 6-thioguanine (6-TG), are widely used in the treatment of cancer, inflammatory conditions and organ transplantation patients. Recent work has shown that cells treated with 6-TG and UVA generate ROS, with implied oxidatively generated modification of DNA. In a study of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in renal transplant patients, we provided the first in vivo evidence linking Aza and oxidatively damaged DNA. Using the hOGG1 comet assay we herein demonstrate high levels of 8-oxodG and alkali-labile sites (ALS) in cells treated with biologically relevant doses of 6-TG, or Aza, plus UVA. This damage was induced dose-dependently. Surprisingly, given the involvement of 6-TG incorporation into DNA in its therapeutic effect, significant amounts of 8-oxodG and ALS were induced in quiescent cells, although less than in proliferating cells. We speculate that some activity of hOGG1 towards unirradiated, 6-TG treated cells, implies possible recognition of 6-TG or derivatives thereof. This is the first report to conclusively demonstrate oxidatively damaged DNA in cells treated with thiopurines and UVA. These data indicate that Aza-derived oxidative stress will occur in the skin of patients on Aza, following even low level UVA exposure. This is a probable contributor to the increased risk of non-melanoma skin cancer in these patients. However, as oxidative stress is unlikely to be involved in the therapeutic effects of Aza, intercepting ROS production in the skin could be a viable route by which this side effect may be minimised.Azathioprine and UVA = 8-oxodG 3

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Damage to Isolated DNA Mediated by Singlet Oxygen

Cited by 96 publications

References 31 publications

Formation of 8-Oxo-7,8-dihydro-2‘-deoxyguanosine (8-Oxo-dGuo) by PAH o-Quinones: Involvement of Reactive Oxygen Species and Copper(II)/Copper(I) Redox Cycling

Formation of 8-Oxo-7,8-dihydro-2‘-deoxyguanosine (8-Oxo-dGuo) by PAH o-Quinones: Involvement of Reactive Oxygen Species and Copper(II)/Copper(I) Redox Cycling

Changes in the Spin State and Reactivity of Cytochrome c Induced by Photochemically Generated Singlet Oxygen and Free Radicals

Combination of azathioprine and UVA irradiation is a major source of cellular 8-oxo-7,8-dihydro-2′-deoxyguanosine

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