Investigation of the genotoxic effects of fluoride on a bone tissue model
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Toxicol Res. https://doi.org/10.1007/s43188-020-00039-0
Toxicological Research
ORIGINAL ARTICLE
Investigation of the genotoxic effects of fluoride on a bone tissue model V. P. Volobaev1 · E. S. Serdyukova2 · E. E. Kalyuzhnaya1 · E. A. Schetnikova1 · A. D. Korotkova1 · A. A. Naik1 · S. N. Bach1 · A. Y. Prosekov1 · A. V. Larionov1 Received: 24 September 2019 / Revised: 14 January 2020 / Accepted: 23 January 2020 © Korean Society of Toxicology 2020
Abstract Fluorides are thought to be a major cause of osteocarcinogenesis, due to their widespread industrial use, ability to accumulate in bone tissue, and genotoxic and probable carcinogenic properties. In vitro experiments investigating the genotoxic potential of fluorides in bone tissue models can provide valuable indirect information on their involvement in osteocarcinogenesis. Here, we investigated whether sodium fluoride (NaF) has the ability to induce DNA damage and chromosomal abnormalities in human osteosarcoma cells after 48 and 72 h of exposure. The cell cultures were treated with NaF in concentrations of 0, 20, 100 and 200 μg/ml. The level of DNA damage was assessed by the comet assay, and the frequency of chromosomal abnormalities by a micronucleus test. A significant increase in DNA damage indicators was noted in the samples treated with fluoride concentrations of 100 and 200 µg/ml, after 48 and 72 h of exposure. The micronucleus test revealed a dose-dependent increase in cells with micronuclei, nucleoplasmic bridges and nuclear protrusions. Increasing the concentration of NaF led to an increase in the prevalence of cytogenetic indicators after both treatment durations. This demonstrated ability of fluorine to exert genotoxic effects on bone cells indirectly indicates the possible importance of fluoride in the aetiology of osteosarcoma. Keywords Genotoxicity · NaF · In vitro · DNA comets · Micronucleus test
Introduction Despite their relative rarity, primary oncological diseases of bone tissue pose a significant problem for modern biomedicine. Along with these cancers being therapeutically challenging, the causes of pathology also remain uncertain. Determining the aetiology of this type of disease is thus an important issue, as knowing its cause(s) will allow us to achieve significant progress in prevention and treatment. The main factor in the development of osteocarcinogenesis is believed to be environmental exposure. Fluorides are thought to be the environmental factors, due to their widespread industrial use, ability to accumulate in bone tissue [1], and genotoxic [2] and probable carcinogenic properties [3, 4]. This assumption is based on previous ecological-epidemiological studies [5] and studies of the correlation * V. P. Volobaev [email protected] 1
Department of Genetics, Kemerovo State University, Krasnaya St 6, Kemerovo, Russia 650000
Tomsk State University, Lenin Avenue, 36, Tomsk, Russia 634050
2
of fluoride in sera with the frequency of oncogenic mutations of the p53 gene in human tumour tissues [6]. However, some publicati
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