| Glutathione and ascorbate are negatively correlated with oxidative DNA damage in human lymphocytes. | |
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MedLine Citation:
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PMID: 10223188 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Intracellular antioxidants, glutathione and ascorbate, and two molecular markers of oxidative DNA damage, 5-hydroxy-2'-deoxycytidine (5-OH-dCyd) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo), were measured in lymphocytes from 105 healthy volunteers. The analysis of 5-OH-dCyd and 8-oxo-dGuo was carried out by HPLC with electrochemical detection such that both compounds were detected on the same chromatography run. There was no significant difference in oxidative DNA damage when the extraction of DNA from cells using phenol was carried out under anaerobic conditions or in the presence of metal ion chelators. This indicates that auto-oxidation of DNA during sample preparation was minimal. Using the above methods, the average level of oxidative DNA damage in lymphocytes was 2.9 +/- 1.4 for 5-OH-dCyd and 4.5 +/- 1.8 for 8-oxo-dGuo lesions per 10(6) dGuo (n = 105). It is unlikely that artifactual oxidation contributed to the observed damage because the level of 5-OH-dCyd was comparable with that of 8-oxo-dGuo in lymphocyte DNA, whereas 8-oxo-dGuo outnumbers 5-OH-dCyd by a ratio of >5:1 when DNA is exposed to various oxidants, including ionizing radiation or Fenton reagents. Rather, the nearly equal levels of 5-OH-dCyd and 8-oxo-dGuo in cellular DNA implies that 8-oxo-dGuo may be more efficiently removed by DNA repair. Finally, and most importantly, the correlation of our endpoints revealed that the naturally occurring level of intracellular antioxidants was negatively correlated to the level of oxidative DNA damage with the strongest correlation observed for glutathione and 8-oxo-dGuo (r = -0.36; P < 0.001). These results strongly suggest that intracellular glutathione and ascorbate protect human lymphocytes against oxidative DNA damage. |
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Authors:
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K J Lenton; H Therriault; T Fülöp; H Payette; J R Wagner |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Carcinogenesis Volume: 20 ISSN: 0143-3334 ISO Abbreviation: Carcinogenesis Publication Date: 1999 Apr |
Date Detail:
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Created Date: 1999-05-20 Completed Date: 1999-05-20 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 607-13 Citation Subset: IM |
Affiliation:
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Centre de recherche, Institut Universitaire de Gériatrie de Sherbrooke, Québec, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Anaerobiosis Antioxidants / analysis* Ascorbic Acid / analysis*, physiology Biological Markers Chelating Agents / pharmacology Chemical Fractionation / methods Chromatography, High Pressure Liquid DNA / chemistry, isolation & purification DNA Damage* Deoxycytidine / analogs & derivatives, analysis Deoxyguanosine / analogs & derivatives, analysis Female Glutathione / analysis*, physiology Granulocytes / chemistry Humans Jurkat Cells / chemistry Lymphocytes / chemistry* Male Middle Aged Monocytes / chemistry Oxidation-Reduction Oxidative Stress Oxygen / chemistry, pharmacology Reference Values Solvents / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Biological Markers; 0/Chelating Agents; 0/Solvents; 50-81-7/Ascorbic Acid; 52278-77-0/5-hydroxy-2'-deoxycytidine; 70-18-8/Glutathione; 7782-44-7/Oxygen; 88847-89-6/8-oxo-7-hydrodeoxyguanosine; 9007-49-2/DNA; 951-77-9/Deoxycytidine; 961-07-9/Deoxyguanosine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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