70 Ks K K1/10 NaF RT-PCR RNA SDS Ta UV Keratin(s) Keratins numbered and classified by (Moll et al. 1982) Sodium fluoride Reverse transcription-polymerase chain reaction Ribonucleic acid Sodium dodecyl sulfate Annealing time Ultraviolet Introduction Application of fluoride is a major reason for the decline of dental caries during the last century. Fluoride increases the resistance of mineralized tissues towards acid demineralization, interferes with the formation of dental plaque microorganisms, and promotes mineralization of incipient lesions. The carioprotective effect of fluorides was found to be dual at pre-eruptive (systemic) and post-eruptive (topical) conditions (Hellwig and Lennon 2004). Fluoride-containing products for topic use range up to 100 mg/100 g of excipient and above. These high fluoride concentrations were innocuous for oral soft tissue in clinical studies (Walsh et al. 2010), because the contact with fluoride lasts only for a few minutes. On the other hand, overexposure to fluoride may have dramatic effects ranging from acute, life-threatening poisoning to chronic dental or skeletal fluorosis encompassing tissue malformations. In the domain of epithelial cell biology, fluoride at high doses was shown to have deleterious effects on pulmonary, gastrointestinal, and renal cell functions (Whitford 1990; Thrane et al. 2001; Partanen 2002). Exposure doses depend on the fluoride concentrations in drinking water and nutrients, on local applications for dental care, and on consumption of medical products and anesthetics. On the cell level, low fluoride doses promote osteoblast proliferation, stimulating bone formation in vitro and in vivo (Farley et al. 1988; Wergedal et al. 1988; Lau et al. 1991). The proliferative activity of fluoride in osteoblasts and also in ameloblasts is biphasic, being mitogenic at micromolar doses but inhibitory for mitosis at millimolar levels. Cell responses to fluoride depend on the cell type; thus, Cell Biol Toxicol (2011) 27:69–81 human keratinocytes survive doses up to 10 mM, whereas ameloblasts at doses as low as 10 μM show significant increase in apoptosis (Dogan et al. 2002; Yan et al. 2007). Adversary effects of high fluoride doses on tissue formation were related to cell toxicity, i.e., necrosis, induction of apoptosis, and reduced cell proliferation, all having negative influences on the formation and functioning of tissues. The fluoride-induced regula- tion of cell proliferation involved the activated protein kinase (MAPK) mitogenic pathway in osteoblasts as well as in lung epithelial cells (Thrane et al. 2001). The influence of fluoride also involved the Rho/ ROCK pathway in murine ameloblasts (Li et al. 2005). It is likely that many protein effectors can be influenced by fluoride, since multiple enzyme activities in the cytoplasm of diverse cell types, e.g., lactate dehydrogenase anhydrase, serine/threonine phosphatase, and adenylate cyclase, are affected (Hodge and Smith 1977; ten Cate 1999). Fluoride has been associated with cell stress, characterized by the induction of chaperon proteins and antioxidant components. The state of stress is thought of as an intersection, in which the cell decides to proceed to apoptosis or to revert to the original state (Bevilacqua et al. 2010). Stress granules appear in the cytoplasm, containing stored messenger ribonucleic acid (mRNA) as well as chaperon proteins (Kedersha and Anderson 2007), in order to help the fast recovery of cells after stress relieve. However, fluoride may also change the transcrip- tome of cultured odontoblasts without the induction of stress markers and without effects on cell prolifer- ation or survival. An altered transcription pattern of tissue-forming components may thereby compromise cell communication and extracellular matrix forma- tion (Wurtz et al. 2008). Beside mineralized tissues, fluoride also affects epithelial structures, for example, in kidney and lung. However, effects on epithelium formation in general and keratinocytes in particular remain largely non- elucidated. Nevertheless, these cells are often exposed to high fluoride doses. In the oral cavity, the lining stratified epithelium is subjected to high doses of fluoride in different forms including toothpaste, mouthwash, and chewing gum. Lung epithelia are exposed to fluoride from the air (Thrane et al. 2001), and kidney epithelia secrete fluoride that has been ingested for different reasons (Dominguez et al. 1991;