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In humans, excessive intake of fluoride may cause dental and skeletal fluorosis. However, endemic fluorosis does not appear to develop in a proportion of individuals exposed to the same levels of fluoride. The mechanisms by which mammalian cells resist fluoride are still unclear. In this study, we developed strains of mouse L\u2010929 cells resistant to different levels of fluoride. High\u2010throughput RNA\u2010sequencing analyses of the fluoride\u2010resistant L\u2010929 cells indicated that massive changes in global gene expression occurred, compared with the wild\u2010type L\u2010929 cells. The main biological processes and functions changed were associated with the extracellular region and matrix, response to stress, receptor binding, and signal transduction. This indicated that high doses of fluoride not only exerted stress on L\u2010929 cells but also induced functional pathways that helped them adapt to the presence of fluoride or to expel it. These data should prove useful in identifying cellular processes or transporters\/channels that play central roles in adaptation to or expulsion of fluoride in humans.<\/jats:p>","DOI":"10.1002\/2211-5463.12236","type":"journal-article","created":{"date-parts":[[2017,5,8]],"date-time":"2017-05-08T15:42:40Z","timestamp":1494258160000},"page":"968-980","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Fluoride resistance capacity in mammalian cells involves complex global gene expression changes"],"prefix":"10.1002","volume":"7","author":[{"given":"Shujun","family":"Ran","sequence":"first","affiliation":[{"name":"Department of Endodontics and Operative Dentistry Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Stomatology Shanghai 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