Increased uracil misincorporation in lymphocytes from folate-deficient rats

Susan Joyce Duthie, George Grant, S Narayanan

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

The development of certain human cancers has been linked with inadequate intake of folates. The effects of folate deficiency in vivo on DNA stability (strand breakage, misincorporated uracil and oxidative base damage) in lymphocytes isolated from rats fed a diet deficient in folic acid was determined. Because the metabolic pathways of folate and other methyl donors are closely coupled, the effects of methionine and choline deficiency alone or in combination with folate deficiency were determined. Feeding male Hooded Lister rats a folate-free diet for 10 weeks created a moderate relate deficiency (25-50% (approx.) decrease in plasma, red blood cell and hepatic folate concentrations (P < 0.05) and a 20% rise in plasma homocysteine (P < 0.05)). Lymphocyte DNA strand breakage was increased successively in all groups after 4 weeks and 8 weeks on the diet (50-100% (approx.) after 8 weeks). Only low folate specifically and progressively induced uracil misincorporation throughout the study (100% (approx.) after 8 weeks). Neither folate deficiency nor choline/methionine deficiency altered oxidative DNA base damage. in summary, moderate folate deficiency in vivo is associated with a decrease in DNA stability, measured as increased DNA strand breakage and misincorporated uracil. (C) 2000 Cancer Research Campaign http://www.bjcancer.com.

Original languageEnglish
Pages (from-to)1532-1537
Number of pages6
JournalBritish Journal of Cancer
Volume83
Issue number11
DOIs
Publication statusPublished - Dec 2000

Keywords

  • folic acid deficiency
  • methyl-donor deficiency
  • rat lymphocytes
  • misincorporated uracil
  • oxidized DNA bases
  • DNA INSTABILITY
  • APOPTOSIS
  • CANCER
  • CELLS
  • BREAKAGE
  • GENE
  • SUPPLEMENTATION
  • CARCINOGENESIS
  • DAMAGE
  • REPAIR
  • oxidized DNA bases

Cite this