| Inhalative Exposure to Vanadium Pentoxide Causes DNA Damage in Workers: Results of a Multiple End Point Study Veronika A. Ehrlich,1 Armen K. Nersesyan,1 Kambis Atefie,1 Christine Hoelzl,1 Franziska Ferk,1 Julia Bichler,1 Eva Valic,2 Andreas Schaffer,3 Rolf Schulte‑Hermann,1 Michael Fenech,4 Karl‑Heinz Wagner,5 and Siegfried Knasmüller1 1Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria; 2Austrian Workers Compensation Board, Vienna, Austria; 3Department of Medicine II, Medical University of Vienna, Vienna, Austria; 4Commonwealth Scientific and Industrial Research Organisation, Human Nutrition, Adelaide, Australia; 5Department of Nutritional Sciences, University of Vienna, Austria Abstract
Background: Inhalative exposure to vanadium pentoxide (V2O5) causes lung cancer in rodents. Objective: The aim of the study was to investigate the impact of V2O5 on DNA stability in workers from a V2O5 factory. Methods: We determined DNA strand breaks in leukocytes of 52 workers and controls using the alkaline comet assay. We also investigated different parameters of chromosomal instability in lymphocytes of 23 workers and 24 controls using the cytokinesis-block micronucleus (MN) cytome method. Results: Seven of eight biomarkers were increased in blood cells of the workers, and vanadium plasma concentrations in plasma were 7-fold higher than in the controls (0.31 µg/L) . We observed no difference in DNA migration under standard conditions, but we found increased tail lengths due to formation of oxidized purines (7%) and pyrimidines (30%) with lesion-specific enzymes (formamidopyrimidine glycosylase and endonuclease III) in the workers. Bleomycin-induced DNA migration was higher in the exposed group (25%) , whereas the repair of bleomycin-induced lesions was reduced. Workers had a 2.5-fold higher MN frequency, and nucleoplasmic bridges (NPBs) and nuclear buds (Nbuds) were increased 7-fold and 3-fold, respectively. Also, apoptosis and necrosis rates were higher, but only the latter parameter reached statistical significance. Conclusions: V2O5 causes oxidation of DNA bases, affects DNA repair, and induces formation of MNs, NPBs, and Nbuds in blood cells, suggesting that the workers are at increased risk for cancer and other diseases that are related to DNA instability. Key words: comet assay, cytokinesis-block micronucleus assay, DNA damage, occupational exposure, vanadium pentoxide. Environ Health Perspect 116:1689–1693 (2008) . doi:10.1289/ehp.11438 available via http://dx.doi.org/ [Online 31 July 2008]
Address correspondence to S. Knasmüller, Institute for Cancer Research, Borschkegasse 8a, 1090 Vienna, Austria. Telephone: 43-1-4277-65142. Fax: 43-1-4277-6519. E-mail: siegfried.knasmueller@meduniwien.ac.at This project was supported by the Austrian Workers Compensation Board, Vienna, Austria. The authors declare they have no competing financial interests. Received 3 March 2008 ; accepted 31 July 2008. An erratum is posted online at http://www.ehponline.org/docs/2009/117-1/errata.html.
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