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Assessment of the in vivo genotoxicity of vanadate: Analysis of micronuclei and DNA damage induced in mice by oral exposure

TitleAssessment of the in vivo genotoxicity of vanadate: Analysis of micronuclei and DNA damage induced in mice by oral exposure
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2005
AuthorsLeopardi, P., Villani Paola, Cordelli Eugenia, Siniscalchi E., Veschetti E., and Crebelli R.
JournalToxicology Letters
Volume158
Pagination39-49
ISSN03784274
KeywordsAdministration, animal cell, animal experiment, animal model, animal tissue, Animals, article, Bioavailability, Bone and Bones, bone marrow, Bone Marrow Cells, cell population, chromatin structure, Chromosome-Defective, Comet Assay, controlled study, DNA, DNA damage, DNA determination, Dose-Response Relationship, Drinking, drinking water, Drug, exposure, Flow cytometry, fluid intake, Gene expression, gene induction, genotoxicity, Inbred Strains, lethargy, male, Mice, Micronuclei, micronucleus, Micronucleus Tests, mouse, Mutagens, nonhuman, observation, Oral, Organ Size, priority journal, Reticulocytes, soft tissue, sperm, Spermatozoa, Spleen, spleen cell, statistical significance, testis, testis cell, vanadate sodium, Vanadates, vanadium, water supply, weight reduction
Abstract

Vanadium compounds are able to interact with living cells exerting a variety of biological effects. The pentavalent form is the most stable and toxic form of the element. In systems in vitro pentavalent vanadium is an effective genotoxic agent, inducing DNA damage and chromosome malsegregation at low doses. On the other hand, no adequate in vivo data are available for the characterization of the genotoxic hazard following oral intake, the most relevant route of human exposure. In this study, the genotoxic effects produced by the oral intake of sodium ortho-vanadate (Na3VO4) were investigated. Male CD-1 mice were treated for 5 weeks with a range of concentrations of Na3VO4 in drinking water (0.75-1500 mg/l). Both micronuclei and primary DNA lesions as detected by comet assay were assessed in several tissues. Statistically significant increases of micronuclei in bone marrow were observed in mice receiving the two highest concentrations of Na3VO4 (750 and 1500 mg/l). A significant increase of comet tail length was observed in splenocytes of mice receiving Na 3VO4 at 1500 mg/l, whereas no effect was observed in bone marrow and testis cells. No treatment-related effect on sperm chromatin structure or on testis cell population was observed. The determination of vanadium content in mouse tissues at the end of treatment highlighted a very low internal exposure, especially in soft tissues. Overall, the results obtained indicate that the genotoxic activity of pentavalent vanadium is expressed in vivo only following high dose exposure, possibly as a consequence of the poor bioavailability of the element. © 2005 Elsevier Ireland Ltd. All rights reserved.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-21344441967&doi=10.1016%2fj.toxlet.2005.02.009&partnerID=40&md5=4db6b7a34bff6a399926f4b0ee75212e
DOI10.1016/j.toxlet.2005.02.009
Citation KeyLeopardi200539