{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T07:49:56Z","timestamp":1773301796258,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T00:00:00Z","timestamp":1524009600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:p>Folate deficiency causes megaloblastic anemia and neural tube defects, and is also associated with some cancers. <jats:italic>In vitro<\/jats:italic>, folate deficiency increases mutation frequency and genome instability, as well as exacerbates the mutagenic potential of known environmental mutagens. Conversely, it remains unclear whether or not elevated folic acid (FA) intakes are beneficial or detrimental to the induction of DNA mutations and by proxy human health. We used the MutaMouse transgenic model to examine the <jats:italic>in vivo<\/jats:italic> effects of FA deficient, control, and supplemented diets on somatic DNA mutant frequency (MF) and genome instability in hematopoietic cells. We also examined the interaction between FA intake and exposure to the known mutagen <jats:italic>N<\/jats:italic>\u2010ethyl\u2010<jats:italic>N<\/jats:italic>\u2010nitrosourea (ENU) on MF. Male mice were fed the experimental diets for 20 weeks from weaning. Half of the mice from each diet group were gavaged with 50 mg\/kg body weight ENU after 10 weeks on diet and remained on their respective diet for an additional 10 weeks. Mice fed a FA\u2010deficient diet had a 1.3\u2010fold increase in normochromatic erythrocyte micronucleus (MN) frequency (<jats:italic>P<\/jats:italic>\u2009=\u20090.034), and a doubling of bone marrow <jats:italic>lacZ<\/jats:italic> MF (<jats:italic>P<\/jats:italic>\u2009=\u20090.035), compared to control\u2010fed mice. Mice exposed to ENU showed significantly higher bone marrow <jats:italic>lacZ<\/jats:italic> and <jats:italic>Pig\u2010a<\/jats:italic> MF, but there was no effect of FA intake on ENU\u2010induced MF. These data indicate that FA deficiency increases mutations and MN formation in highly proliferative somatic cells, but that FA intake does not mitigate ENU\u2010induced mutations. Also, FA intake above adequacy had no beneficial or detrimental effect on mutations or MN formation. Environ. Mol. Mutagen. 59:366\u2013374, 2018. \u00a9 2018 Her Majesty the Queen in Right of Canada 2018.<\/jats:p>","DOI":"10.1002\/em.22190","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T13:33:09Z","timestamp":1524058389000},"page":"366-374","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Folate deficiency increases chromosomal damage and mutations in hematopoietic cells in the transgenic mutamouse model"],"prefix":"10.1002","volume":"59","author":[{"given":"Danielle P.","family":"LeBlanc","sequence":"first","affiliation":[{"name":"Nutrition Research Division, Health Canada Ottawa Canada"},{"name":"Department of Biology Carleton University Ottawa Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie A.","family":"Behan","sequence":"additional","affiliation":[{"name":"Nutrition Research Division, Health Canada Ottawa Canada"},{"name":"Department of Biology 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