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

  • Fiona Caple (a1) (a2) (a3), Elizabeth A. Williams (a2) (a4), Alison Spiers (a1) (a2), John Tyson (a2) (a5), Brian Burtle (a1), Ann K. Daly (a6), John C. Mathers (a2) (a5) and John E. Hesketh (a1) (a2)...
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.

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Corresponding author
*Corresponding author: Professor John E. Hesketh, fax +44 191 222 7424, email j.e.hesketh@ncl.ac.uk
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12S Riso , F Visioli , D Erba , (2004) Lycopene and vitamin C concentrations increase in plasma and lymphocytes after tomato intake. Effects on cellular antioxidant protection. Eur J Clin Nutr 58, 13501358.

22P Moller & S Loft (2006) Dietary antioxidants and beneficial effect on oxidatively damaged DNA. Free Rad Biol Med 41, 388415.

25J Mathers , J Coxhead & J Tyson (2007) Nutrition and DNA repair – potential molecular mechanisms of action. Curr Cancer Drug Targets 7, 425431.

38I Hamann , T Schwerdtle & A Hartwig (2009) Establishment of a non-radioactive cleavage assay to assess the DNA repair capacity towards oxidatively damaged DNA in subcellular and cellular systems and the impact of copper. Mutat Res 669, 122130.

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British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
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