Novel repair action of vitamin C upon in vivo oxidative DNA damage.
There appears to be a paucity of data examining the effect of dietary antioxidants on levels of oxidative DNA damage in vivo, limiting evidence-based assessment of antioxidant efficacy, mechanisms and recommendation for optimal intake. We have examined levels of 8-oxo-2'-deoxyguanosine (8-oxodG) in mononuclear cell DNA, serum and urine from subjects undergoing supplementation with 500 mg/day vitamin C. Significant decreases in DNA levels of 8-oxodG were seen, correlating strongly with increases in plasma vitamin C concentration. Furthermore we established a timecourse for sequential, significant increases in serum and urinary 8-oxodG levels. These results illustrate, for the first time in humans, the kinetics of 8-oxodG removal and processing in vivo, suggesting a role for vitamin C in the regulation of DNA repair enzymes and thereby demonstrating a non-scavenging antioxidant effect.
Cooke
M S
MS
Division of Chemical Pathology, Centre for Mechanisms of Human Toxicity, University of Leicester, UK. msc5@le.ac.uk
Evans
M D
MD
Podmore
I D
ID
Herbert
K E
KE
Mistry
N
N
Mistry
P
P
Hickenbotham
P T
PT
Hussieni
A
A
Griffiths
H R
HR
Lunec
J
J
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000097:blood / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D019587:Dietary Supplements; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress
D000975:Antioxidants; D006151:Guanosine; C046215:8-hydroxyguanosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D001205:Ascorbic Acid