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Genotoxic effects of metals on human salivary gland tissue and lymphocytes as detected by the Comet assay
Authors:Ulrich Harréus MD  PhD  Philipp Baumeister  Norbert Kleinsasser  Maximilian Reiter  Beatrice Bachmeier  Christoph Matthias
Institution:1. Department of Otolaryngology–Head and Neck Surgery , Ludwig-Maximilians-University , 81377, Munich, Germany uli.harreus@med.uni-muenchen.de;3. Department of Otolaryngology–Head and Neck Surgery , Ludwig-Maximilians-University , 81377, Munich, Germany;4. Department of Otolaryngology–Head and Neck Surgery , Julius-Maximilians-University , 97080, Wuerzburg, Germany;5. Department of Clinical Chemistry and Clinical Biochemistry , Ludwig-Maximilians-University , 80336, Munich, Germany
Abstract:The etiology of salivary gland malignancies still remains unclear. Metal compounds are of special interest since they show ubiquitous presence in the environment, are present in many working places, and are accepted (co-)carcinogens in some other malignancies. Metals enter the body as xenobiotics by inhalation or ingestion. This study investigated the genotoxic potential of sodium dichromate (Na2Cr2O7), nickel sulfate (NiSO4), cadmium sulfate (CdSO4) and zinc chloride (ZnCl2) on human salivary gland cells and lymphocytes. Macroscopically healthy tissue of salivary glands was harvested from 46 patients during surgery and isolated to single cells by enzymatic digestion. The cells were incubated with Na2Cr2O7, NiSO4, CdSO4 or ZnCl2. Na2Cr2O7 was also incubated in combination with the other metal compounds listed. Carcinogenic and co-carcinogenic effects of cadmium were tested by incubation with Na2Cr2O7 and consecutive repair intervals. DNA damage and repair were evaluated by the Comet assay, determining DNA-strand breaks. The extent of damage was quantified using a digital analysis system. Na2Cr2O7 produced significantly enhanced DNA-strand breaks in human salivary gland tissue and lymphocytes. All other metal compounds exerted no damaging effect on both cell types. Co-incubation of Na2Cr2O7 with the other metals revealed a significant additive effect only for CdSO4. Specific analysis of the influence of cadmium showed a reduction of DNA-repair after Na2Cr2O7-induced strand breaks in salivary gland cells. This study provides evidence that exposure to distinct metals may significantly contribute to malignant salivary gland tumors. In consequence, further studies as epidemiological and toxicological data are warranted to determine the role of distinct metals as potential (co-) carcinogens.
Keywords:Genotoxicity  metals  human salivary glands  lymphocytes  Comet assay
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