Skip to main content
SpringerLink
Log in

The lack of genotoxicity of sodium fluoride in a battery of cellular tests

  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

In a comprehensive assessment of genotoxicity, sodium fluoride was evaluated in a battery of cellular tests providing different genetic end points and biotransformation capabilities. The tests included the following: rat hepatocyte primary culture/DNA repair assay, Salmonella typhimurium histidine locus reversion assay, adult rat liver epithelial cell/hypoxanthine guanine phosphoribosyl transferase mutation assay, and sister chromatid exchange in two target cell types, human peripheral blood lymphocytes and Chinese hamster ovary cells. Negative findings were made in all assays, indicating that sodium fluoride is not genotoxic in these assays.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ARL:

adult rat liver epithelial cell

CHO:

Chinese hamster ovary cell

HGPRT:

hypoxanthineguanine phosphoribosyl transferase

HPBL:

human peripheral blood lymphocyte

HPC:

hepatocyte primary culture

SCE:

sister chromatid exchange

References

  • AMES, B.N., McCANN, J. and YAMASAKI, E. (1975). Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsomes mutagenicity test. Mutat. Res. 31:347–364.

    Google Scholar 

  • ARMEL, P. and WILLIAMS, G.M. (1987). The molecular nature of spontaneous and chemically induced mutations in the hypoxanthine guanine phosphoribosyl transferase gene in rat liver epithelial cell. Submitted for publication.

  • ASHBY, J. and ISHIDATE Jr., M. (1986). Clastogenicity in vitro of the Na, K, Ca and Mg salts of saccharin; and of magnesium chloride; consideration of significance. Mutat. Res. 163:63–73.

    Google Scholar 

  • CASPARY, W.J., MYHR, B., BOWERS, L., McGREGOR, D., RIACH, C. and BROWN, A. (1987). Mutagenic activity of fluorides in mouse lymphoma cells. Mutat. Res. 187:165–180.

    Google Scholar 

  • COLE, J., MURIEL, W.J. and BRIDGES, B.A. (1986). The mutagenicity of sodium fluoride to L5178Y (wild-type and TK ± (372c)) mouse lymphoma cells. Mutagenesis 1:157–167.

    Google Scholar 

  • GOTO, K., AKEMATSU, T., SHIMAZU, J. and SUGIYAMA, T. (1975). Simple differential Giemsa staining of sister chromatids after treatment with photosensitive dyes and exposure to light and the mechanism of staining. Chromosoma 53:223–230.

    Google Scholar 

  • GRANDJEAN, P., JUEL, K. and JENSEN, O.M. (1985). Mortality and cancer morbidity after heavy occupational fluoride exposure. Am. J. Epidemiol. 121:57–64.

    Google Scholar 

  • HODGE, H.C. (1950). The concentration of fluorides in drinking water to give the point of minimum caries with maximum safety. Am. J. Dent. Assoc. 40:436–439.

    Google Scholar 

  • HOROWITZ, S.H. (1973). A review of systemic and topical fluorides for the prevention of dental caries. Community Dent. Oral Epidemiol. 1:104–114.

    Google Scholar 

  • KRAM, D., SCHNEIDER, E.L., SINGER, L. and MARTIN, G.R. (1978). The effects of high and low fluoride diets on the frequencies of sister chromatid exchanges. Mutat. Res. 57:51–55.

    Google Scholar 

  • LI, Y., DUNIPACE, A.J. and STOOKEY, G.K. (1987). Absence of mutagenic and antimutagenic activity of fluoride in Ames Salmonella Assay. Mutation Res. 190:229–236.

    Google Scholar 

  • MARTIN, G.R., BROWN, K.S., MATHESON, D.W., LEBOWITZ, H., SINGER, L. and OPHAUG, R. (1979). Lack of cytogenetic effects in mice or mutations in Salmonella receiving sodium fluoride. Mutation Res. 66:159–167.

    Google Scholar 

  • MASLANSKY, C.J. and WILLIAMS, G.M. (1981). Evidence for an epigenetic mode of action in organochlorine pesticide hepatocarcinogenicity: A lack of genotoxicity in rat, mouse, and hamster hepatocytes. J. Toxicol. Environ. Health 8:121–130.

    Google Scholar 

  • MENZER, E.R. and NELSON, J.O. (1986). Water and Soil Pollutants. In: Casarett and Doull's Toxicology, C.D. Klaassen, M.O. Amdur and J. Doull, Eds. pp. 846. Macmillan Publishing Co., N.Y., N.Y.

    Google Scholar 

  • NATIONAL RESEARCH COUNCIL. (1977). Drinking Water and Health. National Academy of Sciences. Washington, D.C. Vol, 1, pp. 369–400 and pp. 433–435.

    Google Scholar 

  • NATIONAL RESEARCH COUNCIL. (1980). Drinking Water and Health. National Academy of Sciences. Washington, D.C., Vol. 3, pp. 279–283.

    Google Scholar 

  • PERRY, P.E. and EVANS, H.J. (1975). Cytological detection of mutagen-carcinogen exposure by SCE. Nature 258:121–125.

    Google Scholar 

  • ROGERS, A.W. (1973) In: Techniques of Autoradiography. Elsevier Scientific Publishing Co., pp. 218.

  • SCHAAPER, R.M., KOPLITZ, R.M., TKESHELASHVILI, L.K. and LOEB, L.A. (1987). Metal-induced lethality and mutagenesis: Possible role of apurinic intermediates. Mutat. Res. 177:179–188.

    Google Scholar 

  • SHIMADA, T., SWANSON, A.F., LEBER, P. and WILLIAMS, G.M. (1985). Activities of chlorinated ethane and ethylene compounds in the Salmonella/rat microsome mutagenesis and rat hepatocyte/DNA repair assay under vapor phase exposure conditions. Cell Biol. Toxicol. 1:159–180.

    Google Scholar 

  • SIROVER, M.A. and LOEB, L.A. (1976). Metal-induced infidelity during DNA synthesis. Proc. Natl. Acad. Sci. USA 73:2331–2335.

    Google Scholar 

  • SKARE, J.A., SCHROTEL, K.R. and NIXON, G.A. (1986a). Lack of DNA-strand breaks in rat testicular cells after in vivo treatment with sodium fluoride. Mutat. Res. 170:85–92.

    Google Scholar 

  • SKARE, J.A., WONG, T.K., EVANS, B.L.B. and CODY, D.B. (1986b). DNA-repair studies with sodium fluoride: comparative evaluation using density gradient ultracentrifugation and autoradiography. Mutat. Res. 172:77–87.

    Google Scholar 

  • SUNDERMAN, F.W., Jr. (1979). Mechanism of metal mutagenesis. Biol. Trace Elem. Res. 1:63–85.

    Google Scholar 

  • SUGIMURA, T. and NEGAO, M. (1980). Modification of mutagenic activity. In: Chemical Mutagens, F.J. de Serres and A. Hollander, Eds. Vol. VI, pp. 41–60. Plenum Press, New York.

    Google Scholar 

  • TELANG, S., TONG, C. and WILLIAMS, G.M. (1982). Epigenetic membrane effects of a possible tumor promoting type on cultured liver cells by the nongenotoxic organochlorine pesticides chlordane and heptachlor. Carcinogenesis 3:1175–1178.

    Google Scholar 

  • THOMSON, E.J., KILANOWSKI, F.M. and PERRY P.E. (1985). The effect of fluoride on chromosome aberration and sister-chromatid exchange frequencies in cultured human lymphocytes. Mutat. Res. 144:89–92.

    Google Scholar 

  • TONG, C., FAZIO, M., TELANG, S., and WILLIAMS, G.M. (1980). The detection of genotoxic chemicals in the adult rat liver epithelial cell/hypoxanthine-guanine phosphoribosyl transferase (ARL/HGPRT) mutagenesis assay. Ann. N.Y. Acad. Sci. 349:407–408.

    Google Scholar 

  • TONG, C., FAZIO, M. and WILLIAM, G.M. (1981). Rat hepatocyte-mediated mutagenesis of human cells by carcinogenic polycyclic aromatic hydrocarbons but not orgnaochlorine pesticides. Proc. Soc. Expt. Biol. Med. 167:572–575.

    Google Scholar 

  • TONG, C., LASPIA, M.F., TELANG, S. and WILLIAMS, G.M. (1981a). The use of adult rat liver cultures in the detection of genotoxicity of various polycyclic aromatic hydrocarbons. Environ. Mutat. 3:477–487.

    Google Scholar 

  • TONG, C. and WILLIAMS, G.M. (1978). Introduction of purine analog resistant mutants in rat liver epithelial lines by metabolic activation dependent and independent carcinogens. Mutat. Res. 58:339–352.

    Google Scholar 

  • TONG, C. and WILLIAMS, G.M. (1979). Variation in response in the adult rat liver epithelial cell/hypoxanthine-guanine phosphoribosyl transferase (ARL/HGPRTase) mutation assay with different metabolic activation-dependent carcinogens. Environ. Mutat. 3:148.

    Google Scholar 

  • TONG, C. and WILLIAMS, G.M. (1980). Definition of conditions for the detection of genotoxic chemicals in the adult rat liver epithelial cells/hypoxanthine-guanine phosphoribosyltransferase (ARL/HGPRT) mutagenesis assay. Mutat. Res. 74:1–9.

    Google Scholar 

  • TONG, C., VED BRAT, S. and WILLIAMS, G.M. (1981b). Sister chromatid exchange induction by polycyclic aromatic hydrocarbons in an intact cell system of adult rat liver epithelial cells. Mutat. Res. 91:467–473.

    Google Scholar 

  • TONG, C., VED BRAT, S., GILL, R., SHIMADA, T. and WILLIAMS, G.M. (1985). Evaluation of genotoxicity of beryllium, cadmium, chromium, and nickel in an in vitro battery. Environmental Mutagenesis 7(Suppl. 3):64.

    Google Scholar 

  • TSUTSUI, T., SUZUKI, N., OHMORI, M. and MAIZUMI, H. (1984a). Cytotoxicity, chromosome aberrations and unscheduled DNA synthesis in cultured human diploid fibroblasts induced by sodium fluoride. Mutat. Res. 139:193–198.

    Google Scholar 

  • TSUTSUI, T., SUZUKI, N. and OHMORI, M. (1984b). Sodium fluoride-induced morphological and neoplastic transformation, chromosome aberrations, sister chromatid exchanges, and unscheduled DNA synthesis in cultured Syrian hamster embryo cells. Cancer Res. 44:938–941.

    Google Scholar 

  • TSUTSUI, T., IDE, K. and MAIZUMI, H. (1984c). Induction of unscheduled DNA synthesis in cultured human oral kerationcytes by sodium fluoride. Mutat. Res. 140:43–48.

    Google Scholar 

  • WEISBURGER, J.H. and WILLIAMS, G.M. (1981). Carcinogen testing, current problems and new approaches. Science 214:401–407.

    Google Scholar 

  • WILLIAMS, G.M. and GUNN, J.M. (1974). Long-term cell culture of adult rat liver epithelial cells. Exp. Cell Res. 89:139–142.

    Google Scholar 

  • WILLIAMS, G.M. (1976a). Primary and long-term culture of adult rat liver epithelial cells. Methods Cell Biol. 14:357–364.

    Google Scholar 

  • WILLIAMS, G.M. (1976b). Carcinogen-induced DNA repair in primary rat liver cell cultures: A possible screen for chemical carcinogens. Cancer Lett. 1:231–236.

    Google Scholar 

  • WILLIAMS, G.M. (1977). Detection of chemical carcinogens by unscheduled DNA synthesis in rat primary cell cultures. Cancer Res. 37:1845–1851.

    Google Scholar 

  • WILLIAMS, G.M. (1981). The detection of genotoxic chemicals in the hepatocyte primary culture/DNA repair test. GANN 27:45–55.

    Google Scholar 

  • WILLIAMS, G.M. and WEISBURGER, J.H. (1986). Chemical Carcinogens. In: Casarett and Doull's Toxicology, C.D. Klaassen, M.O. Amdur and J. Doull, Eds., pp. 99–173. Macmillan Publishing Co., New York.

    Google Scholar 

  • WILLIAMS, G.M. and WEISBURGER, T.H. (1987). Application of the cellular test battery in the decision point approach to carcinogen testing. Mutation Res., in press.

  • WILLIAMS, G.M., BERMUDEZ, E. and SCARAMUZZINO, D. (1977). Rat hepatocyte primary cell cultures. III. In Vitro 13:809–817.

    Google Scholar 

  • WILLIAMS, G.M., LASPIA, M.F. and DUNKEL, V.C. (1982). Reliability of the hepatocyte primary culture/DNA repair test in testing of coded carcinogens and noncarcinogens. Mutat. Res. 97:359–370.

    Google Scholar 

Download references

Author information

Author notes

  1. Charles C. Tong

    Present address: Biological Services Division, United States Testing Company, Inc., 1415 Park Avenue, 07030, Hoboken, NJ

  2. Sharma Ved Brats

    Present address: Braton Biotech, Inc., 1 Taft Court, 20850, Rockville, MD

Authors and Affiliations

  1. American Health Foundation, Valhalla, New York

    Charles C. Tong, Charlene A. McQueen, Sharma Ved Brats & Gary M. Williams

Authors
  1. Charles C. Tong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Charlene A. McQueen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sharma Ved Brats
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gary M. Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tong, C.C., McQueen, C.A., Ved Brats, S. et al. The lack of genotoxicity of sodium fluoride in a battery of cellular tests. Cell Biol Toxicol 4, 173–186 (1988). https://doi.org/10.1007/BF00119244

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00119244

Key words

Search

Navigation