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.
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Fluoride does not induce DNA breakage in Chinese hamster ovary cells in vitro
Fluoride has been widely used in dentistry because it is a specific and effective caries prophylactic agent. However, excess fluoride may represent a hazard to human health, especially by causing injury to genetic material. Genotoxicity tests represent an important part of cancer research to assess the risk of potential carcinogens.
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Cytogenetic effects of sodium fluoride
Sodium fluoride (NaF) is widely used for the prevention of dental caries at various concentrations. The clastogenic effect of NaF has been tested by the use of several cytogenetic assay systems, but the findings on its genotoxicity are not consistent. In this study, the effects of NaF on chromosomes, unscheduled
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Mutagenic effect of hydrogen fluoride on animals
The mutagenic effect of hydrogen fluoride in concentration 1.0 mg/m-3 was studied in rats and mice. Prolonged inhalation of this compound increased the frequency of cells with chromosome abnormalities in the bone marrow of albino rats. The mutagenic effect was higher in older animals. No dominant-lethal effect was observed in
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Sodium fluoride and chromosome damage (in vitro human lymphocyte and in vivo micronucleus assays)
The clastogenic potential of sodium fluoride was determined both in vitro (using cultured human lymphocytes) and in vivo (using the rat bone-marrow micronucleus test). The incidence of chromosome aberrations in human lymphocyte cultures exposed to 20 or 40 micrograms/ml sodium fluoride (3 and 9% respectively) was significantly increased compared with
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Is fluoride a mutagen?
Recent studies suggest that fluoride may be genotoxic. While the concentration of fluoride in artificially fluoridated water (1 mg Fl-1) is generally considered to be "safe", levels of fluoride present in a number of widely used dental health products, such as fluoride-containing toothpaste, appear to be potentially mutagenic. Since fluoride
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Fluoride/Osteosarcoma Link Is Biologically Plausible
The "biological plausiblility" of a fluoride-osteosarcoma link is widely acknowledged in the scientific literature. The biological plausibility centers around three facts: 1) Bone is the principal site of fluoride accumulation, particularly during the growth spurts of childhood; 2) Fluoride is a mutagen when present at sufficient concentrations, and 3) Fluoride can stimulate the proliferation of osteoblasts (bone-forming cells).
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Fluoride & Osteosarcoma: A Timeline
Several human epidemiological studies have found an association between fluoride in drinking water and the occurrence of osteosarcoma (bone cancer) in young males. These studies are consistent with the National Toxicology Program's (NTP) cancer bioassay which found that fluoride-treated male rats had an dose-dependent increase in osteosarcoma. Although a number of studies have failed to detect an association between fluoride and osteosarcoma, none of these studies have measured the risk of fluoride at specific windows in time, which based on recent results, is the critical question with respect to fluoride and osteosarcoma.
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NTP Bioassay on Fluoride/Cancer (1990)
In 1977, the U.S. Congress requested that animal studies be conducted to determine if fluoride can cause cancer. The result of the Congressional request was an extensive animal study conducted in the 1980s by the National Toxicology Program (NTP) and published in 1990. The main finding of NTP's study was a dose-dependent increase in osteosarcoma (bone cancer) among the fluoride-treated male rats.
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Fluoride's Mutagenicity: In vivo Studies
Consistent with dozens of in vitro studies, a number of in vivo studies, in both humans and animals, have found evidence of fluoride-induced genetic damage. In particular, research on humans exposed to high levels of fluoride have found increased levels of "sister chromatid exchange" (SCE). As noted in one study: "In
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Fluoride's Mutagenicity: In vitro Studies
According to the National Toxicology Program, "the preponderance of evidence" from laboratory "in vitro" studies indicate that fluoride is a mutagenic compound. Many substances which are mutagens, are also carcinogens (i.e. they can cause cancer). As is typical for in vitro studies, the concentrations of fluoride that have generally been tested
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