A comparison of folic acid deficiency-induced genomic instability in lymphocytes of breast cancer patients and normal non-cancer controls from a Chinese population in Yunnan

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dc.contributor.authorWang, X.
dc.contributor.authorWu, X.
dc.contributor.authorLiang, Z.
dc.contributor.authorHuang, Y.
dc.contributor.authorFenech, M.
dc.contributor.authorXue, J.
dc.date.issued2006
dc.description.abstractWe hypothesized that the genomic response to folate deficiency might be different between breast cancer cases and healthy subjects. To test this hypothesis, we performed a comprehensive study on the genotoxic and cytotoxic effects of in vitro folic acid (FA) deficiency on primary human lymphocytes from 19 breast cancer patients and 20 age-matched healthy females from Yunnan, China using the cytokinesis-block micronucleus assay. Lymphocytes from the volunteers were cultured in RPMI1640 medium containing 30, 120 or 240 nM FA for 9 days. The results showed that 30 nM FA was associated with increased frequencies of micronucleated binucleated cell (MNed BNC), nucleoplasmic bridges (NPB), nuclear buds (BUD), apoptosis (APO) and necrosis (NEC) relative to 120 and 240 nM FA (P<0.001) in lymphocytes of case and control groups in vitro, however there were no significant differences between the 120 and 240 nM FA within each sampling group. The case group showed significantly higher frequencies of MNed BNC than control at 120 and 240 nM FA (P<0.05-0.001) but not at 30 nM FA (P=0.052). NEC was significantly higher in breast cancer group than control at all concentrations of FA (P<0.005). FA concentration explained 60, 39, 39, 52 and 71% of the variance of MNed BNC, NPB, BUD, APO and NEC, respectively compared with breast cancer status which only explained 6 and 7% of the variance of MNed BNC and NEC(Two way ANOVA, P<0.0001). Difference of difference analysis showed that breast cancer cases were not abnormally sensitive to the genome-damaging effect of folate deficiency. We concluded that (i) increased concentrations of FA abolished the genome-damaging effect of FA deficiency in lymphocytes of both breast cancer patients and controls to a similar extent and (ii) FA concentration is much more important than breast cancer status in determining genomic instability and cell death.
dc.description.statementofresponsibilityWang, Xu ; Wu, Xiayu ; Liang, Ziqing ; Huang, Yunchao ; Fenech, Michael ; Xue, Jinglun
dc.identifier.citationMutagenesis, 2006; 21(1):41-47
dc.identifier.doi10.1093/mutage/gei069
dc.identifier.issn0267-8357
dc.identifier.issn1464-3804
dc.identifier.orcidFenech, M. [0000-0002-8466-0991]
dc.identifier.urihttp://hdl.handle.net/2440/22768
dc.language.isoen
dc.publisherOxford Univ Press
dc.source.urihttps://doi.org/10.1093/mutage/gei069
dc.subjectBreast
dc.subjectLymphocytes
dc.subjectMicronuclei, Chromosome-Defective
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectFolic Acid Deficiency
dc.subjectGenomic Instability
dc.subjectNecrosis
dc.subjectFolic Acid
dc.subjectCase-Control Studies
dc.subjectMicronucleus Tests
dc.subjectCytokinesis
dc.subjectApoptosis
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectPopulation Groups
dc.subjectChina
dc.subjectFemale
dc.titleA comparison of folic acid deficiency-induced genomic instability in lymphocytes of breast cancer patients and normal non-cancer controls from a Chinese population in Yunnan
dc.typeJournal article
pubs.publication-statusPublished

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