biostudies-literatureSharma RNIDCR NIH HHSe10895https://www.ebi.ac.uk/biostudies/studies/S-EPMC2878349biostudies-literatureUnknown5(5)<h4>Background</h4>It is not known why the ameloblasts responsible for dental enamel formation are uniquely sensitive to fluoride (F(-)). Herein, we present a novel theory with supporting data to show that the low pH environment of maturating stage ameloblasts enhances their sensitivity to a given dose of F(-). Enamel formation is initiated in a neutral pH environment (secretory stage); however, the pH can fall to below 6.0 as most of the mineral precipitates (maturation stage). Low pH can facilitate entry of F(-) into cells. Here, we asked if F(-) was more toxic at low pH, as measured by increased cell stress and decreased cell function.<h4>Methodology/principal findings</h4>Treatment of ameloblast-derived LS8 cells with F(-) at low pH reduced the threshold dose of F(-) required to phosphPloS oneThe acid test of fluoride: how pH modulates toxicity.PMC2878349DE018106R01 DE018106Skobe ZTsuchiya MSharma RTannous BABartlett JDfalseThe acid test of fluoride: how pH modulates toxicity.<h4>Background</h4>It is not known why the ameloblasts responsible for dental enamel formation are uniquely sensitive to fluoride (F(-)). Herein, we present a novel theory with supporting data to show that the low pH environment of maturating stage ameloblasts enhances their sensitivity to a given dose of F(-). Enamel formation is initiated in a neutral pH environment (secretory stage); however, the pH can fall to below 6.0 as most of the mineral precipitates (maturation stage). Low pH can facilitate entry of F(-) into cells. Here, we asked if F(-) was more toxic at low pH, as measured by increased cell stress and decreased cell function.<h4>Methodology/principal findings</h4>Treatment of ameloblast-derived LS8 cells with F(-) at low pH reduced the threshold dose of F(-) required to phosph2010-01-01T00:00:00Z2010 May2026-05-09T03:15:43.748Z2019-03-26T23:07:33ZS-EPMC28783492053194410.1371/journal.pone.0010895