{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T01:27:37Z","timestamp":1784251657316,"version":"3.55.0"},"reference-count":64,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,8,28]],"date-time":"2013-08-28T00:00:00Z","timestamp":1377648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:p>Alzheimer's disease is associated with accumulation of extracellular beta amyloid peptide 42 (A\u03b242) which may induce DNA damage and reduce cellular regenerative potential. These effects may be exacerbated under conditions of folate deficiency. The aim of this study was to investigate whether extracellular A\u03b242 induces DNA damage and cell death in human peripheral lymphocytes and whether there is an interactive effect between extracellular A\u03b242 and folic acid status. Peripheral blood lymphocytes were cultured in medium under conditions of both low and high folate (20 and 200 nM, respectively) and challenged with either A\u03b242 or the physiologically normal form A\u03b240 (both at 5, 10, 15 \u00b5M). Genome stability and cytotoxicity events were investigated using the cytokinesis\u2010block micronucleus cytome (CBMN\u2010cyt) assay. Outcome measures scored included the nuclear division index (NDI), necrosis, apoptosis, binucleated cells with micronuclei (MN), nucleoplasmic bridges (NPB), and nuclear buds (NBUD) and abnormally shaped nuclei (circular, (CIR) and horse\u2010shoe, (HS) that may be indicative of mitotic disruption. Folic acid deficiency significantly reduced NDI (<jats:italic>P<\/jats:italic> &lt; 0.001) and increased all the DNA damage biomarkers (MN, NPB, NBUD, HS, CIR), (<jats:italic>P<\/jats:italic> &lt; 0.001). In contrast, exposure to A\u03b240 had no impact on CBMN cytome biomarkers but A\u03b242 significantly reduced NDI (<jats:italic>P<\/jats:italic> &lt; 0.01), increased necrosis (<jats:italic>P<\/jats:italic> &lt; 0.05) and frequency of cells with circular nuclei (<jats:italic>P<\/jats:italic> &lt; 0.01). There was no evidence of an interaction between A\u03b242 and folic acid with respect to CBMN cytome biomarkers. Extracellular A\u03b242 appears to have cytotoxic and cytostatic effects but its effect on chromosomal instability appears to be small relative to folate deficiency. Environ. Mol. Mutagen. 55:1\u201314, 2014. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/em.21811","type":"journal-article","created":{"date-parts":[[2013,8,28]],"date-time":"2013-08-28T06:36:38Z","timestamp":1377671798000},"page":"1-14","source":"Crossref","is-referenced-by-count":14,"title":["Extracellular amyloid beta 42 causes necrosis, inhibition of nuclear division, and mitotic disruption under both folate deficient and folate replete conditions as measured by the cytokinesis\u2010block micronucleus cytome assay"],"prefix":"10.1002","volume":"55","author":[{"given":"Sau Lai","family":"Lee","sequence":"first","affiliation":[{"name":"Commonwealth Scientific and Industrial Research Organisation, (Animal, Food and Health Sciences) Adelaide South Australia 5000"},{"name":"Discipline of Physiology School of Medical Sciences, The University of Adelaide Adelaide South Australia 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