Low levels of p53 mutations in Indian patients with osteosarcoma and the correlation with fluoride levels in bone Journal Article


Authors: Balakrishnamurthy, P.; Pillai, K. S.; Ramesh, N.; Stanley, V. A.; Desai, B. S.; Natarajan, M.
Article Title: Low levels of p53 mutations in Indian patients with osteosarcoma and the correlation with fluoride levels in bone
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.
Keywords: osteosarcoma; adolescent; adult; child; clinical article; human tissue; school child; bone neoplasms; gene mutation; gene sequence; sequence analysis; exon; polymerase chain reaction; dna damage; protein p53; carcinogenesis; dna, neoplasm; india; bone and bones; dna mutational analysis; dna primers; bioaccumulation; electrophoretic mobility; genes, p53; p53 mutation; chemical carcinogenesis; fluorides; humans; human; male; female; priority journal; article; bone fluoride; bone level
Journal Title: Journal of Environmental Pathology, Toxicology and Oncology
Volume: 20
Issue: 3
ISSN: 0731-8898
Publisher: Begell House, Inc  
Date Published: 2001-01-01
Start Page: 237
End Page: 243
Language: English
PUBMED: 11797833
PROVIDER: scopus
DOI: 10.1615/JEnvironPatholToxicolOncol.v20.i3.80
DOI/URL:
Notes: Export Date: 21 May 2015 -- Source: Scopus
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