REACTIVE OXYGEN SPECIES, NITRIC OXIDE, AND INTRACELLULAR Ca2+ PARTICIPATE IN FLUORIDE-INDUCED YEAST CELL DEATH.

Numerous studies have indicated that the chronic intake of an excessive dose of fluoride has harmful physiological effects and fluorosis has been confirmed in some models. However, the mechanism underlying fluorosis has not been elucidated. In this study, we investigated the mechanism of fluoride-induced yeast cell death. For this, cultured yeast cells were treated with sodium fluoride (NaF) at concentrations of 0, 15, 30, 60, 90, 120, and 150 mM NaF for up to 24 hr. The results showed that NaF inhibits yeast cell growth, reduces cell viability, inhibits cell division, and increases the levels of reactive oxygen species (ROS), nitric oxide (NO), and intracellular Ca2+ in yeast cells. The inhibitory effect of NaF on yeast cells is blocked by antioxidants (ascorbic acid), Ca2+ antagonists (EGTA), and NO scavengers (hemoglobin). Taken together, these results indicate that intracellular ROS, NO, and Ca2+ participate in NaF-induced yeast cell death. Our findings elucidate the signal transduction pathways mediating the toxicity of fluoride, a common drinking water contaminant, and provides strong evidence that is relevant tor the study of the effects of fluoride on humans and the protection of humans from fluoride damage. [ABSTRACT FROM AUTHOR]