Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/54964
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Type: Journal article
Title: Folate deficiency induces aneuploidy in human lymphocytes in vitro - evidence using cytokinesis-blocked cells and probes specific for chromosomes 17 and 21
Author: Wang, X.
Thomas, P.
Xue, J.
Fenech, M.
Citation: Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 2004; 551(1-2):167-180
Publisher: Elsevier Science BV
Issue Date: 2004
ISSN: 1386-1964
0027-5107
Statement of
Responsibility: 
Xu Wang, Philip Thomas, Jinglun Xue and Michael Fenech
Abstract: Folate plays a critical role in the prevention of chromosome breakage and hypomethylation of DNA. Deficiency in this vitamin may lead to demethylation of heterochromatin causing structural centromere defects that could induce abnormal distribution of replicated chromosomes during nuclear division. Because aneuploidy of chromosomes 17 and 21 is often observed in breast cancer and leukaemia and increased risk for these cancers is associated with folate deficiency, we hypothesized that folate deficiency may lead to aneuploidy of chromosomes 17 and 21. To test these hypotheses we cultured lymphocytes from eight female volunteers (aged 40-48 years) in RPMI 1640 medium containing 12 or 120nM of folic acid (FA) or 5-methyltetrahydrofolate (MF) for 9 days. Chromosomes 17 and 21 aneuploidies induced by folate deficiency were measured in mononucleated (MONO) and cytokinesis-blocked binucleated (BN) lymphocytes after dual-color fluorescent in situ hybridization (FISH) with a digoxigenin-labeled probe for the alphoid satellite sequence of chromosome 17 and a biotin-labeled probe for the pericentric region of chromosome 21. The results showed that 12nm of MF or FA caused a significant 26-35% increment in frequency of aneuploidy of chromosome 17 (P = 0.0017) and aneupoidy of chromosome 21 (P = 0.0008) relative to 120nM MF or FA. The pattern of aneuploidy in binucleated cells was significantly correlated with that observed in mononucleated cells (R = 0.51-0.75, P < 0.0004) and was consistent with a model based on chromosome loss or partial aneusomy rescue as the cause rather than non-disjunction, although the latter mechanism could not be excluded. MF was not more efficient than FA in preventing aneuploidy in this in vitro system. We conclude that folate deficiency is a risk factor for chromosomes 17 and 21 aneuploidy.
Keywords: Lymphocytes; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 21; Humans; Folic Acid Deficiency; Aneuploidy; Folic Acid; Riboflavin; In Situ Hybridization, Fluorescence; Micronucleus Tests
Description: Copyright © 2004 Elsevier B.V. All rights reserved.
RMID: 0020091976
DOI: 10.1016/j.mrfmmm.2004.03.008
Description (link): http://www.elsevier.com/wps/find/journaldescription.cws_home/506092/description#description
Appears in Collections:Pharmacology publications

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