Fluoride Resistance Research Articles

On the role of cyclic AMP in the cytotoxic effect of fluoride.

The possible role of adenosine 3',5'-monophosphate (cAMP) in the cytotoxic effect of fluoride was investigated in fluoride sensitive mouse fibroblasts (LS) and a subline of LS resistant to 6 mM fluoride (FR6). In both cell lines, growth was inhibited by dibutyryl-cAMP, prostaglandin (PG)E2 and theophylline, FR6 being somewhat more sensitive to these agents than LS. FR6 had lower basal cAMP levels in the intact cells and lower basal adenylate cyclase activity in the homogenate preparation than LS, but the percentual response of intact cells or adenylate cyclase preparations to PGE1 or PGE2 was about the same in the two cell lines, and the sensitivity of the adenylate cyclase to fluoride was similar. No measurable increase in cAMP content was found in either LS or FR6 after exposure of the intact cells to various concentrations of fluoride for various times. The present results indicate that the development of fluoride resistance in these cells is not due to decreased sensitivity to cAMP, and probably not due to altered cAMP-formation in response to fluoride. The growth inhibitory and cytotoxic effects of fluoride in LS cells is probably not mediated through cAMP.

Fluoride, fluoride resistance and glycolysis in cultured cells.

Long-term (several years) exposure to fluoride induced decreased production of lactate in cultured, fluoride resistant LS cells. In intact, sensitive cells, 6 mM NaF had no effect on glycolysis, whereas in homogenates, from both resistant and sensitive cells, lactate production was blocked by 6 mM NaF, indicating the cell membrane to be a barrier to fluoride. A lower intracellular rather than extracellular fluoride concentration was found in the sensitive cell with a ratio of 0.4, whereas fluoride resistant cells excluded fluoride from their intracellular milieu.

Histochemical study of a fluoride resistant acid phosphatase reaction in the mouse duodenum.

A fluoride resistant acid phosphatase reaction (pH 5.0) has been demonstrated histochemically in the cuticular border of the mouse duodenum. This reaction was shown to be inactivated by the metal chelating agent, ethylene diamine tetraacetic acid, and reactivated by the following metallic salts : calcium chloride, cobalt(ous) nitrate, cupric sulfate, ferric chloride, ferric ammonium sulfate, ferrous sulfate, lead nitrate, lithium sulfate, magnesium sulfate, mercuric chloride, manganous chloride and zinc acetate. The two ferric salts produced the greatest amount of reactivation and cupric sulfate and manganous chloride produced the least amount of reactivation. These characteristics of inactivation by a metal chelating agent and metal reactivation plus the fluoride resistance of the acid phosphatase reaction present in the cuticular border of the mouse duodenum are features more typical of an alkaline type of phosphatase rather than the acid variety. This suggests that alkaline type phosphatase may be demonstrable histochemically in the cuticular border of the mouse duodenum in the acid pH range.