NDLI: Exocyclic DNA adducts in sheep with skeletal fluorosis resident in the proximity of the Portoscuso-Portovesme industrial estate on Sardinia Island, Italy

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Exocyclic DNA adducts in sheep with skeletal fluorosis resident in the proximity of the Portoscuso-Portovesme industrial estate on Sardinia Island, Italy

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Toxicology Research Vol - 4 Issue - 3

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Exocyclic DNA adducts in sheep with skeletal fluorosis resident in the proximity of the Portoscuso-Portovesme industrial estate on Sardinia Island, Italy

Content Provider	Royal Society of Chemistry (RSC)
Author	Farigu, Serafina Peluso, Marco E. M. Biggeri, Annibale Rocca, Stefano Giese, Roger W. Leoni, Antonio Munnia, Armelle Catelan, Dolores Bruzzone, Marco Ceppi, Marcello
Copyright Year	2015
Abstract	The mechanisms by which fluoride produces its toxic effects are still not clear. Therefore, we conducted a cross-sectional study to evaluate the fluoride-induced toxicity on randomly selected sheep with skeletal fluorosis resident near the large non-ferrous metallurgy Portoscuso-Portovesme industrial estate and the Carbonia and Gonnessa towns (control district) with respect to animals from a remote site without industrial settlements, on Sardinia Island, Italy. We measured the prevalence of 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M1dG) adducts, a biomarker of oxidative stress and lipid peroxidation, in the soft organs of the study animals using the 32P-postlabelling assay. Then, we analysed the association between M1dG adducts and sheep-farm localization. In addition, cadmium and lead levels were measured in the same matrices by mass spectrometry. The histopathology analysis showed that the sheep resident near the industrial site and in the control district presented typical manifestations of fluorosis. The statistical analyses using log-normal regression models indicated that there was a significant association between exocyclic DNA adducts and skeletal fluorosis. The mean ratios, adjusted for age, of renal and hepatic M1dG for the sheep with fluorosis were 5.09, 95% C.I. 1.67–15.53 and 2.04, 95% C.I. 0.91–4.57, p = 0.009 and p = 0.078, respectively. After stratification for sheep-farm localization, the renal and hepatic levels of M1dG adducts were significantly higher in the sheep resident near the industrial estate as compared to controls. Intermediate amounts of DNA damage were observed in the kidney of the sheep living in the control district. As expected, the levels of cadmium and lead were significantly increased in the sheep with fluorosis as compared to controls. Also, the concentrations of heavy metals were driven from the distance of the sheep-farms to the industrial site. Our results broaden knowledge about the role of exocyclic DNA adducts in the etiology of skeletal fluorosis. Fluoride generated from the non-ferrous metallurgy complexes may increase the intracellular amounts of oxidative stress and ROS within the soft organs. A continuous attack to DNA may contribute to the general decline of cellular functions, ranging from disturbance of DNA metabolism, triggering cell-cycle arrest and apoptosis, to inducing necrosis and cellular degenerative changes.
Starting Page	986
Ending Page	993
Page Count	8
File Format	HTM / HTML PDF
ISSN	2045452X
Volume Number	4
Issue Number	4
Journal	Toxicology Research
DOI	10.1039/c5tx00045a
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Oxidative stress Cadmium Biomarker Reactive oxygen species Sardinia Lipid peroxidation Carbonia Regression analysis Metabolism Kidney Necrosis Sardinia Island Fluoride Deoxyguanosine Histopathology Log-normal distribution Carbonia, Sardinia DNA Italy Skeletal fluorosis Metallurgy Gonnessa Mass spectrometry Apoptosis
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Toxicology

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