Endoscopy 2005; 37 - 4
DOI: 10.1055/s-2005-868527

DNA replication biomarkers as functional markers of folate status in colon cells

AP McGlynn 1, GR Wasson 1, SL O'Reilly 2, A Molloy 2, I Bradbury 1, JJ Strain 1, JM Scott 2, CS Downes 1, H McNulty 1, DG Weir 3
  • 1Centre for Molecular Biosciences, University of Ulster, Coleraine, Northern Ireland
  • 2Department of Biochemistry, Trinity College, Dublin 2, Ireland
  • 3Dept. of Clinical Medicine, St. James' Hospital, Dublin

Aims: To develop new methods based on modifications of Comet assay to investigate DNA biomarkers (uracil misincorporation and DNA hypomethylation) as putative functional markers of folate status in colonocytes.

Methods: Biopsies from the polyp, adjacent to polyp and 10cm distal to polyp were analysed from cases harbouring polyps (n=56). Biopsies from normal colon were analysed from polyp-free controls (n=64). Individuals harbouring colonic adenomas (n=20) were also randomised to receive folic acid (600mg daily) or placebo for 6 months post polypectomy. Systemic and colonocyte folate, and colonocyte DNA biomarkers, were evaluated in case-control and intervention subjects.

Results: In the case-control study, cases had lower colonocyte folate, but not systemic folate, than controls (p<0.001). Uracil misincorporation was higher in the adenomas compared with either hyperplastic polyp cases (p<0.001) or controls (p<0.001). No difference in global DNA hypomethylation was identified. Folic acid supplementation resulted in a strong trend towards increased colonocyte folate (p=0.071) and decreased uracil misincorporation (p=0.081) in the polyp site, but not in the area distal to polyp. Neither global nor gene-specific hypomethylation showed any response.

Conclusions: Uracil misincorporation was found to be a more predictive folate-sensitive marker of DNA metabolic malfunction in colon carcinogenesis, than DNA hypomethylation.