Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers

G. P. Basten, Susan Joyce Duthie, Lynn Peters Pirie, Nicholas James Vaughan, M. H. Hill, H. J. Powers

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65 Citations (Scopus)

Abstract

We have previously reported that supplementation with folic acid (1.2 mg day(-1) for 12 week) elicited a significant improvement in the folate status of 61 healthy volunteers. We have examined effects of this supplement on markers of genomic stability. Little is known about the effect of folate supplementation on DNA stability in a cohort, which is not folate deficient. Preintervention, there was a significant inverse association between uracil misincorporation in lymphocyte DNA and red cell folate (P < 0.05). In contrast, there were no associations between folate status and DNA strand breakage, global DNA methylation or DNA base excision repair (measured as the capacity of the lymphocyte extract to repair 8-oxoGua ex vivo). Folate supplementation elicited a significant reduction in uracil misincorporation ( P < 0.05), while DNA strand breakage and global DNA methylation remained unchanged. Increasing folate status significantly decreased the base excision repair capacity in those volunteers with the lowest preintervention folate status (P < 0.05). Uracil misincorporation was more sensitive to changes in folate status than other measures of DNA stability and therefore could be considered a specific and functional marker of folate status, which may also be relevant to cancer risk in healthy people.

Original languageEnglish
Pages (from-to)1942-1947
Number of pages6
JournalBritish Journal of Cancer
Volume94
Issue number12
Early online date30 May 2006
DOIs
Publication statusPublished - 19 Jun 2006

Keywords

  • folic acid
  • health
  • uracil misincorporation
  • DNA damage
  • HAMSTER OVARY CELLS
  • FOLIC-ACID SUPPLEMENTATION
  • DONOR-DEFICIENT RATS
  • URACIL MISINCORPORATION
  • METHYLENETETRAHYDROFOLATE REDUCTASE
  • IN-VITRO
  • S-ADENOSYLMETHIONINE
  • CONTROLLED-TRIAL
  • COMMON MUTATION
  • COMET ASSAY

Cite this

Basten, G. P., Duthie, S. J., Pirie, L. P., Vaughan, N. J., Hill, M. H., & Powers, H. J. (2006). Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers. British Journal of Cancer, 94(12), 1942-1947. https://doi.org/10.1038/sj.bjc.6603197