{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:11:14Z","timestamp":1790989874195,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T00:00:00Z","timestamp":1643068800000},"content-version":"vor","delay-in-days":24,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005104","name":"Australian Institute of Health and Welfare, Australian Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005104","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Type 2 diabetes (T2D) is associated with elevated frequencies of micronuclei (MNi) and other DNA damage biomarkers. Interestingly, individuals with T2D are more likely to be deficient in micronutrients (folic acid, pyridoxal-phosphate, cobalamin) that play key roles in one-carbon metabolism and maintaining genomic integrity. Furthermore, it has recently been shown that deficiencies in these nutrients, in particular folic acid leaves cells susceptible to glucose-induced DNA damage. Therefore, we sought to investigate if the B lymphoblastoid WIL2-NS cell line cultured under folic acid-deficient conditions was more sensitive to DNA damage induced by glucose, or the reactive glycolytic byproduct methylglyoxal (MGO) and subsequent advanced glycation endproduct formation. Here, we show that only WIL2-NS cultured under folic acid-deficient conditions (23 nmol\/l) experience an increase in MNi frequency when exposed to high concentrations of glucose (45 mmol\/l) or MGO (100 \u00b5mol\/l). Furthermore, we showed aminoguanidine, a well-validated MGO and free radical scavenger was able to prevent further MNi formation in folic acid-deficient cells exposed to high glucose, which may be due to a reduction in MGO-induced oxidative stress. Interestingly, we also observed an increase in MGO and other dicarbonyl stress biomarkers in folic acid-deficient cells, irrespective of glucose concentrations. Overall, our evidence shows that folic acid-deficient WIL2-NS cells are more susceptible to glucose and\/or MGO-induced MNi formation. These results suggest that individuals with T2D experiencing hyperglycemia and folic acid deficiency may be at higher risk of chromosomal instability.<\/jats:p>","DOI":"10.1093\/mutage\/geac003","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T12:27:30Z","timestamp":1641385650000},"page":"24-33","source":"Crossref","is-referenced-by-count":16,"title":["Folic acid deficiency increases sensitivity to DNA damage by glucose and methylglyoxal"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0042-2065","authenticated-orcid":false,"given":"Leigh","family":"Donnellan","sequence":"first","affiliation":[{"name":"University of South Australia, Clinical and Health Sciences, Health and Biomedical Innovation , Adelaide, SA 5000 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley S","family":"Simpson","sequence":"additional","affiliation":[{"name":"University of South Australia, Clinical and Health Sciences, Health and Biomedical Innovation , Adelaide, SA 5000 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varinderpal S","family":"Dhillon","sequence":"additional","affiliation":[{"name":"University of South Australia, Clinical and Health Sciences, Health and Biomedical Innovation , Adelaide, SA 5000 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Costabile","sequence":"additional","affiliation":[{"name":"University of South Australia, Clinical and Health Sciences, Health and Biomedical Innovation , Adelaide, SA 5000 , Australia"},{"name":"University of South Australia, Centre for Cancer Biology and SA Pathology , Frome Road, Adelaide, SA 5000 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Fenech","sequence":"additional","affiliation":[{"name":"University of South Australia, Clinical and Health Sciences, Health and Biomedical Innovation , Adelaide, SA 5000 , Australia"},{"name":"Genome Health Foundation , North Brighton , SA 5048 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6477-9127","authenticated-orcid":false,"given":"Permal","family":"Deo","sequence":"additional","affiliation":[{"name":"University of South Australia, Clinical and Health Sciences, Health and Biomedical Innovation , Adelaide, SA 5000 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,25]]},"reference":[{"key":"2022061012012900700_CIT0001","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.mrfmmm.2011.11.003","article-title":"Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity.","volume":"733","author":"Fenech","year":"2012","journal-title":"Mutat 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