Abstract
The pathogenesis of osteogenic sarcoma is not known. Recently, chronic fluoride exposure has been incriminated as having a possible etiologic role by causing a nonspecific osteoblast proliferation. We were interested in exploring the possible relationship between fluoride bone content and p53 mutations. We analyzed p53 mutations in various exons in tissue of osteosarcoma, and correlated the findings with the bone fluoride levels in Indian patients. We analyzed tissue samples from 20 osteosarcoma patients for possible genetic alterations including mutations, and we assessed the extent of fluoride accumulation in bone. Fragments displaying an altered electrophoretic mobility were confirmed as having mutated sequences. Mutation was observed in samples of two cases (10% incidence). Eighteen samples showed bone fluoride levels between 1000 and 27,000 ppm, whereas the 2 mutated samples showed fluoride levels of 64,000 and 89,000 ppm, respectively. The high levels of bone fluoride levels and the similarity of the mechanisms of action between fluoride-induced DNA damage and chemically-induced p53 mutations lead us to propose that high fluoride bone content might have been one of the major factors causing osteosarcoma.
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Toxicology and Carcinogenesis Studies of Sodium Fluoride in F344/N Rats and B6C3F1 Mice (Drinking Water Studies)
CASRN: 7681-49-4 Chemical Formula: NaF Molecular Weight: 41.99 Report Date: December 1990 Sodium fluoride is a white, crystalline, water-soluble powder used in municipal water fluoridation systems, in various dental products, and in a variety of industrial applications. Toxicology and carcinogenesis studies were conducted with F344/N rats and B6C3F1 mice of each sex by incorporating
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Time trends for bone and joint cancers and osteosarcomas in the Surveillance, Epidemiology and End Results (SEER) Program
At the request of the Committee, we have enclosed a brief description of the time trends for bone and joint cancers and for osteosarcomas in the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute (NCI), and the relationship of these trends to fluoridation of drinking water
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USA: More About Fluoride.
This excerpt was provided free by Science Direct; the full article requires payment. ... The supporting cancer hazard evidence was an animal study sponsored by the government’s National Toxicology Program (Lancet, Feb 3, p 282). Since then, the Public Health Service has responded to this and similar news stories by reaffirming
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Fluoride exposure in public drinking water and childhood and adolescent osteosarcoma in Texas.
PURPOSE: The purpose of this study was to examine the association between fluoride levels in public drinking water and childhood and adolescent osteosarcoma in Texas; to date, studies examining this relationship have been equivocal. Using areas with high and low naturally occurring fluoride, as well as areas with optimal fluoridation,
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An assessment of bone fluoride and osteosarcoma
The association between fluoride and risk for osteosarcoma is controversial. The purpose of this study was to determine if bone fluoride levels are higher in individuals with osteosarcoma. Incident cases of osteosarcoma (N = 137) and tumor controls (N = 51) were identified by orthopedic physicians, and segments of tumor-adjacent
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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 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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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'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 & 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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