Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/56014
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Folic acid deficiency increases chromosomal instability, chromosome 21 aneuploidy and sensitivity to radiation-induced micronuclei |
Author: | Beetstra, S. Thomas, P. Salisbury, C. Turner, J. Fenech, M. |
Citation: | Mutation Research: Fundamental and Molecular Mechanisms of Mutagenesis, 2005; 578(1-2):317-326 |
Publisher: | Elsevier Science BV |
Issue Date: | 2005 |
ISSN: | 1386-1964 0027-5107 |
Statement of Responsibility: | Sasja Beetstra, Philip Thomas, Carolyn Salisbury, Julie Turner and Michael Fenech |
Abstract: | Folic 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. |
Keywords: | B-Lymphocytes Cell Line, Tumor Chromosomes, Human, Pair 21 Micronuclei, Chromosome-Defective Humans Folic Acid Deficiency Aneuploidy Chromosomal Instability Folic Acid Micronucleus Tests Cytokinesis Apoptosis Dose-Response Relationship, Drug Radiation, Ionizing Radiation Tolerance Models, Biological |
Description: | Crown copyright © 2005 |
DOI: | 10.1016/j.mrfmmm.2005.05.012 |
Published version: | http://dx.doi.org/10.1016/j.mrfmmm.2005.05.012 |
Appears in Collections: | Aurora harvest Pharmacology publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.