Fluoride mediates apoptosis in osteosarcoma UMR 106 and its cytotoxicity depends on the pH

• Published in: Archives of toxicology Vol. 72; no. 1; pp. 52 - 58
• Main Authors: HIRANO, S, ANDO, M
• Format: Journal Article
• Language: English
• Published: Berlin Springer 1997
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - genetics; Biological and medical sciences; Bone Neoplasms; Calcimycin - toxicity; Cell Count - drug effects; Cell Line - drug effects; Cell Survival - drug effects; Chemical and industrial products toxicology. Toxic occupational diseases; Culture Media; DNA Fragmentation; Dose-Response Relationship, Drug; Fluorides - antagonists & inhibitors; Fluorides - toxicity; Hydrogen-Ion Concentration; Ionophores - toxicity; Macrophages, Alveolar - drug effects; Medical sciences; Metals and various inorganic compounds; Mice; Necrosis; Osteosarcoma; Rats; Toxicology; Tumor Cells, Cultured - drug effects; Culture medium; Rat; Toxicity; Rodentia; Diseases of the osteoarticular system; Fluorides; In vitro; Vertebrata; Mammalia; Cell death; Animal; pH; Bone; Mechanism of action; Apoptosis
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s002040050468

Although an excess intake of fluoride has been reported to cause skeletal fluorosis, very little is known about the mechanism of adverse effects of fluoride on bone. In the present study cytotoxic effects of fluoride were studied using the osteosarcoma cell line, UMR 106. The DNA ladder formation upon agarose electrophoresis and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining revealed that UMR 106 underwent apoptosis following exposure to 5 mM fluoride for 8 h. On the other hand exposure to A23187, a calcium ionophore, caused necrosis while co-exposure to fluoride and A23187 inhibited fluoride-mediated apoptosis in UMR 106. The proliferation of UMR 106 cells cultured for 6 days in the presence of 0.5 mM fluoride was significantly decreased compared to the control culture. The cytotoxic effects of fluoride were modulated by both the cell density and the pH of the culture medium. The fluoride-induced viability loss in UMR 106 was enhanced in culture of high cell-density and inversely correlated with pH of the culture medium. Enhancement of fluoride cytotoxicity at acidic pH was also observed in rat alveolar macrophages and RAW 264, a macrophage cell line. The results suggest that fluoride-mediated apoptosis and culture conditions, including pH of the medium, should be taken into consideration to evaluate toxicity of fluoride in vitro.