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Folic acid deficiency increases chromosomal instability, chromosome 21 aneuploidy and sensitivity to radiation-induced micronuclei

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dc.contributor.authorBeetstra, S.
dc.contributor.authorThomas, P.
dc.contributor.authorSalisbury, C.
dc.contributor.authorTurner, J.
dc.contributor.authorFenech, M.
dc.date.issued2005
dc.descriptionCrown copyright © 2005
dc.description.abstractFolic acid deficiency can lead to uracil incorporation into DNA, hypomethylation of DNA, inefficient DNA repair and increase chromosome malsegregation and breakage. Because ionising radiation increases demand for efficient DNA repair and also causes chromosome breaks we hypothesised that folic acid deficiency may increase sensitivity to radiation-induced chromosome breakage. We tested this hypothesis by using the cytokinesis-block micronucleus assay in 10 day WIL2-NS cell cultures at four different folic acid concentrations (0.2, 2, 20, and 200 nM) that span the "normal" physiological range in humans. The study showed a significant dose-dependent increase in frequency of binucleated cells with micronuclei and/or nucleoplasmic bridges with decreasing folic acid concentration (P<0.0001, P=0.028, respectively). These biomarkers of chromosomal instability were also increased in cells irradiated (1.5 Gy gamma-rays) on day 9 relative to un-irradiated controls (P<0.05). Folic acid deficiency and gamma-irradiation were shown to have a significant interactive effect on frequency of cells containing micronuclei (two-way ANOVA, interaction P=0.0039) such that the frequency of radiation-induced micronucleated cells (i.e. after subtracting base-line frequency of un-irradiated controls) increased with decreasing folic acid concentration (P-trend<0.0001). Aneuploidy of chromosome 21, apoptosis and necrosis were increased by folic acid deficiency but not by ionising radiation. The results of this study show that folate status has an important impact on chromosomal stability and is an important modifying factor of cellular sensitivity to radiation-induced genome damage.
dc.description.statementofresponsibilitySasja Beetstra, Philip Thomas, Carolyn Salisbury, Julie Turner and Michael Fenech
dc.identifier.citationMutation Research: Fundamental and Molecular Mechanisms of Mutagenesis, 2005; 578(1-2):317-326
dc.identifier.doi10.1016/j.mrfmmm.2005.05.012
dc.identifier.issn1386-1964
dc.identifier.issn0027-5107
dc.identifier.orcidFenech, M. [0000-0002-8466-0991]
dc.identifier.urihttp://hdl.handle.net/2440/56014
dc.language.isoen
dc.publisherElsevier Science BV
dc.source.urihttps://doi.org/10.1016/j.mrfmmm.2005.05.012
dc.subjectB-Lymphocytes
dc.subjectCell Line, Tumor
dc.subjectChromosomes, Human, Pair 21
dc.subjectMicronuclei, Chromosome-Defective
dc.subjectHumans
dc.subjectFolic Acid Deficiency
dc.subjectAneuploidy
dc.subjectChromosomal Instability
dc.subjectFolic Acid
dc.subjectMicronucleus Tests
dc.subjectCytokinesis
dc.subjectApoptosis
dc.subjectDose-Response Relationship, Drug
dc.subjectRadiation, Ionizing
dc.subjectRadiation Tolerance
dc.subjectModels, Biological
dc.titleFolic acid deficiency increases chromosomal instability, chromosome 21 aneuploidy and sensitivity to radiation-induced micronuclei
dc.typeJournal article
pubs.publication-statusPublished

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