title: Sodium fluoride is a less efficient human cell mutagen at low concentrations.
abstract: Sodium fluoride was found to induce gene-locus mutations at the thymidine kinase (tk) and hypoxanthine guanine phosphoribosyl transferase (hgprt) loci in human lymphoblastoid cells. A single, 28 hr exposure to up to 600 micrograms/ml sodium fluoride induced a concentration-dependent increase in mutant fraction at both gene loci and reduced cell survival to 12% relative to negative control cultures. When cells were exposed to sodium fluoride concentrations that were only minimally toxic using a 20 day treatment protocol, no detectable induction of mutation was ob-served at the hgprt locus, and induction of mutation was observed at the tk locus only for treatment with 65 micrograms/ml sodium fluoride; exposure to 50 and 35 micrograms/ml sodium fluoride did not induce detectable mutation. The assay protocol used was of sufficient statistical sensitivity to detect the level of mutation predicted based on a linear extrapolation of data obtained from a 28 hour exposure. The implications of these observations with regard to the extrapolability of mutagenicity data to low concentrations are discussed.
authors.affiliation: Gentest Corporation, Woburn, Massachusetts 01801.
authors.forename: C L
authors.initials: CL
authors.lastname: Crespi
authors.forename: G M
authors.initials: GM
authors.lastname: Seixas
authors.forename: T
authors.initials: T
authors.lastname: Turner
authors.forename: B W
authors.initials: BW
authors.lastname: Penman
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009152:Mutagenicity Tests; D009153:Mutagens; D012969:Sodium Fluoride / Q000494:pharmacology*; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: D009153:Mutagens; D012969:Sodium Fluoride; D013937:Thymidine Kinase