TY - JOUR
T1 - The effects of fluoride on cell migration, cell proliferation, and cell metabolism in GH4C1 pituitary tumour cells
AU - Mendoza-Schulz, A.
AU - Solano-Agama, C.
AU - Arreola-Mendoza, L.
AU - Reyes-Márquez, B.
AU - Barbier, O.
AU - Del Razo, L. M.
AU - Mendoza-Garrido, M. E.
N1 - Funding Information:
We are grateful to Mr. Osbaldo Ríos for technical assistance, and Mrs. Ma. Eugenia Arceo for secretarial assistance. This work was supported by a grant from the National Council of Science and Technology of México (55080).
PY - 2009/10/28
Y1 - 2009/10/28
N2 - The consumption of drinking water rich in fluoride has toxic effects on the central nervous system. In cell biology research, fluoride is currently used as a phosphatase inhibitor. The aim of the present study was to evaluate the effect of fluoride on different physiological processes in GH4C1 pituitary tumour cells. We used a range of different fluoride concentrations, from levels below normal human serum concentrations (0.23 and 1.2 μmol/L) to those observed in chronically exposed persons (10.7 μmol/L) and above (107 and 1072 μmol/L). Treatment of 10.7 μmol/L fluoride resulted in a discrete induction of DNA synthesis, without a change in cell number. Cell migration, a behaviour stimulated by growth factors, was increased in cells treated with 2.4 μmol/L. At this fluoride concentration, changes in phosphorylation status of both cytoskeletal and cytosolic protein fractions, as well as in actin cytoskeletal arrangements were observed. The GH4C1 fluoride treated cells had significantly less cellular protein than control cells, suggesting an effect of fluoride on hormone secretion and protein synthesis in this endocrine cell. The bioreduction of MTT was significantly increased with a wide range of fluoride concentrations. With the highest fluoride concentration, 1072 μmol/L, all of the analysed parameters were significantly reduced, suggesting that this dose is highly toxic in GH4C1 cells. Our results show that biologically relevant concentrations of fluoride are capable of increasing cell migration in tumour cells, suggesting that exposure to fluoride could stimulate tumour invasion.
AB - The consumption of drinking water rich in fluoride has toxic effects on the central nervous system. In cell biology research, fluoride is currently used as a phosphatase inhibitor. The aim of the present study was to evaluate the effect of fluoride on different physiological processes in GH4C1 pituitary tumour cells. We used a range of different fluoride concentrations, from levels below normal human serum concentrations (0.23 and 1.2 μmol/L) to those observed in chronically exposed persons (10.7 μmol/L) and above (107 and 1072 μmol/L). Treatment of 10.7 μmol/L fluoride resulted in a discrete induction of DNA synthesis, without a change in cell number. Cell migration, a behaviour stimulated by growth factors, was increased in cells treated with 2.4 μmol/L. At this fluoride concentration, changes in phosphorylation status of both cytoskeletal and cytosolic protein fractions, as well as in actin cytoskeletal arrangements were observed. The GH4C1 fluoride treated cells had significantly less cellular protein than control cells, suggesting an effect of fluoride on hormone secretion and protein synthesis in this endocrine cell. The bioreduction of MTT was significantly increased with a wide range of fluoride concentrations. With the highest fluoride concentration, 1072 μmol/L, all of the analysed parameters were significantly reduced, suggesting that this dose is highly toxic in GH4C1 cells. Our results show that biologically relevant concentrations of fluoride are capable of increasing cell migration in tumour cells, suggesting that exposure to fluoride could stimulate tumour invasion.
KW - Cell migration
KW - Cell proliferation
KW - Fluoride
KW - GHC pituitary tumour cells
KW - MTT metabolism
UR - http://www.scopus.com/inward/record.url?scp=69549109852&partnerID=8YFLogxK
U2 - 10.1016/j.toxlet.2009.07.014
DO - 10.1016/j.toxlet.2009.07.014
M3 - Artículo
SN - 0378-4274
VL - 190
SP - 179
EP - 186
JO - Toxicology Letters
JF - Toxicology Letters
IS - 2
ER -