Inter-individual variation in DNA damage and base excision repair in young, healthy non-smokers: effects of dietary supplementation and genotype.
Diets rich in fruits and vegetables are associated with lower risk of cancer which may be conferred in part by the antioxidant properties of these foods. However, antioxidant supplementation or increased consumption of antioxidant-rich foods has been reported to have inconsistent effects on DNA damage. The present work (the DART study) investigated the extent of inter-individual variation in DNA damage, the capacity for base excision repair (BER) and the responses of both variables to supplementation with an antioxidant supplement for 6 weeks. There was a wide inter-individual variation in endogenous lymphocyte DNA strand breaks (8-fold variation), in damage after a challenge with H2O2 (16-fold variation) and in DNA repair (41-fold variation) measured using the comet assay. When stratified into tertiles according to the pre-supplementation level of endogenous DNA damage, there was a statistically significant decrease in DNA damage after supplementation in the tertile with the highest pre-supplementation level of damage. There was no effect of supplementation on BER. Endogenous DNA damage level before supplementation was significantly different (P = 0.037) between the three genotypes for the Val16Ala single nucleotide polymorphism in manganese superoxide dismutase (rs4880) with individuals homozygous/wild type showing less damage than those carrying the alanine variant.
Caple
Fiona
F
Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Williams
Elizabeth A
EA
Spiers
Alison
A
Tyson
John
J
Burtle
Brian
B
Daly
Ann K
AK
Mathers
John C
JC
Hesketh
John E
JE
D000293:Adolescent; D000328:Adult; D000409:Alanine; D000975:Antioxidants / Q000008:administration & dosage* / Q000032:analysis; D004247:DNA / Q000097:blood; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004032:Diet; D019587:Dietary Supplements; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012643:Selenium / Q000008:administration & dosage; D013482:Superoxide Dismutase / Q000235:genetics; D014801:Vitamin A / Q000008:administration & dosage; D014810:Vitamin E / Q000008:administration & dosage; D014815:Vitamins / Q000008:administration & dosage
D000975:Antioxidants; D014815:Vitamins; D014801:Vitamin A; D014810:Vitamin E; D004247:DNA; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D012643:Selenium; D000409:Alanine