Increased uracil misincorporation in lymphocytes from folate-deficient rats

Susan Joyce Duthie, George Grant, S Narayanan

Research output: Contribution to journalArticle

57 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

Increased uracil misincorporation in lymphocytes from folate-deficient rats. / Duthie, Susan Joyce; Grant, George; Narayanan, S .

In: British Journal of Cancer, Vol. 83, No. 11, 12.2000, p. 1532-1537.

Research output: Contribution to journalArticle

Duthie, Susan Joyce ; Grant, George ; Narayanan, S . / Increased uracil misincorporation in lymphocytes from folate-deficient rats. In: British Journal of Cancer. 2000 ; Vol. 83, No. 11. pp. 1532-1537.
@article{2d3b5a84d87c481e861229ee30b84d24,
title = "Increased uracil misincorporation in lymphocytes from folate-deficient rats",
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.",
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",
author = "Duthie, {Susan Joyce} and George Grant and S Narayanan",
year = "2000",
month = "12",
doi = "10.1054/bjoc.2000.1481",
language = "English",
volume = "83",
pages = "1532--1537",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "11",

}

TY - JOUR

T1 - Increased uracil misincorporation in lymphocytes from folate-deficient rats

AU - Duthie, Susan Joyce

AU - Grant, George

AU - Narayanan, S

PY - 2000/12

Y1 - 2000/12

N2 - 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.

AB - 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.

KW - folic acid deficiency

KW - methyl-donor deficiency

KW - rat lymphocytes

KW - misincorporated uracil

KW - oxidized DNA bases

KW - DNA INSTABILITY

KW - APOPTOSIS

KW - CANCER

KW - CELLS

KW - BREAKAGE

KW - GENE

KW - SUPPLEMENTATION

KW - CARCINOGENESIS

KW - DAMAGE

KW - REPAIR

KW - oxidized DNA bases

U2 - 10.1054/bjoc.2000.1481

DO - 10.1054/bjoc.2000.1481

M3 - Article

VL - 83

SP - 1532

EP - 1537

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 11

ER -