British Journal of Nutrition

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British Journal of Nutrition (2010), 103:1585-1593 Cambridge University Press
Copyright © The Authors 2009
doi:10.1017/S0007114509993540

Full Papers

Molecular Nutrition

Inter-individual variation in DNA damage and base excision repair in young, healthy non-smokers: effects of dietary supplementation and genotype


Fiona Caplea1a2a3, Elizabeth A. Williamsa2a4, Alison Spiersa1a2, John Tysona2a5, Brian Burtlea1, Ann K. Dalya6, John C. Mathersa2a5 and John E. Hesketha1a2 c1

a1 Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
a2 Human Nutrition Research Centre, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
a3 School of Applied Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK
a4 Human Nutrition Unit, Department of Oncology, University of Sheffield, Sheffield S10 2RX, UK
a5 Institute for Ageing and Health, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
a6 School of Clinical Laboratory Sciences, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
Article author query
caple f [PubMed]  [Google Scholar]
williams ea [PubMed]  [Google Scholar]
spiers a [PubMed]  [Google Scholar]
tyson j [PubMed]  [Google Scholar]
burtle b [PubMed]  [Google Scholar]
daly ak [PubMed]  [Google Scholar]
mathers jc [PubMed]  [Google Scholar]
hesketh je [PubMed]  [Google Scholar]

Abstract

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.

(Received June 17 2009)

(Revised October 16 2009)

(Accepted November 20 2009)

(Online publication January 19 2010)

Key Words:Antioxidants; DNA damage; Base excision repair; Genotypes; Superoxide dismutase

Correspondence:

c1 Corresponding author: Professor John E. Hesketh, fax +44 191 222 7424, email j.e.hesketh@ncl.ac.uk

Footnotes

Abbreviations: BER, base excision repair; FRAP, ferric reducing antioxidant power; NER, nucleotide excision repair; SNP, single nucleotide polymorphisms; TEAC, Trolox total equivalent antioxidant capacity