Document Detail


Glutathione and ascorbate are negatively correlated with oxidative DNA damage in human lymphocytes.
MedLine Citation:
PMID:  10223188     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
K J Lenton; H Therriault; T Fülöp; H Payette; J R Wagner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Carcinogenesis     Volume:  20     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  1999 Apr 
Date Detail:
Created Date:  1999-05-20     Completed Date:  1999-05-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  607-13     Citation Subset:  IM    
Affiliation:
Centre de recherche, Institut Universitaire de Gériatrie de Sherbrooke, Québec, Canada.
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MeSH Terms
Descriptor/Qualifier:
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:
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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