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6 GENOTOXICITY OF FLUORIDE
Pages 91-108

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From page 91...
... IN VITRO GENOTOXICITY TEST SYSTEMS Microbes NaF has been tested extensively for its ability to induce gene mutations in Ames Salmonella typhimurium reverse mutation assay by standard plate and preincubation tests and in other microbial systems, with and without metabolic activation at concentrations ranging from 0. ~ to 4,421 ,ug/plate Fable 6-~.
From page 94...
... Gene Mutations Fluoride has been tested for its mutagenicity in several in vitro mammalian cell systems with ant} without metabolic activation Table 6-~. NaF and KF were strongly mutagenic in the mouse lymphoma L5178Y TK+~- test with and without S9 at concentrations ranging from 10 to 600 ,ug/mL (Cole et al., 1986; Caspary et al., 1987~; the authors speculated that the induced mutant colonies resulted from chromosomal damage ratherthan point (gene)
From page 95...
... or at the 6-tg locus in Chinese hamster ovary V79 cells treated with NaF at 10-400 ~g/mL for 24 hours (Slamenova et al., 1992~. Chromosomal Aberrations and Sister Chromatid Exchanges NaF has been shown to induce chromosomal damage in several in vitro mammalian cell systems (Table 6-2~.
From page 96...
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From page 97...
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From page 98...
... In the NTP studies, the incidence of sister chromatic exchanges was increased in Chinese hamster ovary cells treated with NaF at concentrations up to 1,600 ,ug/mlL with S9. Human Cells Several investigators have reported chromosomal aberrations in cultured human lymphocytes and fibroblasts at NaF concentrations ranging from 20 to 40 ,ug/mL~ (Tsutsui, et al., 1984b; Albanese, 19X7; Scott and Roberts, 1987~.
From page 99...
... Dose-related increases in the frequencies of transformed colonies were observed in Syrian hamster embryo cells at NaF concentrations of 10-125 ,ug/mL (Tsutsui et al., 1984a; Jones et al., 19X8a,b; Lasne et al., 1988~. Morphological transformation was not induced in BALB/3T3 cells treated with NaF for 72 hours at concentra .
From page 100...
... Syrian hamster embryo cells transformed by NaF at 75 or 100 ~g/mL and injected into newborn Syrian hamsters produced tumors at the site of injection after 141-320 days (Tsutsui et al., 1984a)
From page 101...
... reported that NaF in diet induced whole chromosomal loss and partial chromosomal loss, an indication of chromosomal breakage in postmeiotic germ cells of males. However, Gocke et al.
From page 102...
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From page 103...
... Somatic CeUs Induction of sister chromatic exchanges, chromosomal aberrations, and micronuclei was reported in the bone-marrow cells of mice aciministereci NaF at 10-40 mg/kg of body weight by gavage and by intraperitoneal or subcutaneous injection (Ma et al., 1986; Pati anti Bhunya, 19871. However, the study of Ma et al.
From page 104...
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From page 105...
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From page 106...
... Germ Cents In the Mohamed and Chandler (1982) study in which BALB/c mice were given drinking water containing fluoride at 0, I, 5, 10, 50, 100, or 200 mg/1~ for 3-6 weeks, cytological tests showed that NaF at i-200 mg/L induced chromosomal aberrations in spermatocytes in a dosedependent manner.
From page 107...
... A study on sperm-head morphology in Swiss mice exposed intraperitoneally to NaF at 10-40 mg/kg for 5 days and then sampled 35 clays later reported a large dosedependent increase in abnormal sperm (Pati ant} Bhunya, 1987~. However, no morphological abnormalities were observed in sperm from mice that drank water containing fluoride at concentrations of 75 g/L for 21 weeks (Dunipace et al., 1989)
From page 108...
... Fluoride can react with divalent cations in He cell to affect enzyme activities that are necessary for DNA or RNA synthesis or chromosomal metabolism or maintenance; it might react directly with DNA as part of a complex; or it can disrupt other cellular processes, such as cell differentiation or energy metabolism (Hellung-Larsen and Klenow, 1969; Harper et al., 1974; Holland, 1979a,b; Srivastava et al., 1981; Tmai et al., 19X3; Edwards and Parry, 19X6~. A hypothesis of secondary effects on DNA or chromosomes is attractive because there is no apparent mechanism by which many of the genotoxic effects observed can be induced by direct interaction of fluoride with DNA.


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