Assessment of the in vivo genotoxicity of vanadate: analysis of micronuclei and DNA damage induced in mice by oral exposure.
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 (Na(3)VO(4)) were investigated. Male CD-1 mice were treated for 5 weeks with a range of concentrations of Na(3)VO(4) 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 Na(3)VO(4) (750 and 1500 mg/l). A significant increase of comet tail length was observed in splenocytes of mice receiving Na(3)VO(4) 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.
Genetic Toxicology Unit, Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
Paola
P
Leopardi
Paola
P
Villani
Eugenia
E
Cordelli
Ester
E
Siniscalchi
Enrico
E
Veschetti
Riccardo
R
Crebelli
D000284:Administration, Oral; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D020552:Comet Assay; D004247:DNA / Q000032:analysis / Q000187:drug effects*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004326:Drinking; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D012156:Reticulocytes / Q000187:drug effects / Q000473:pathology; D013094:Spermatozoa / Q000187:drug effects / Q000473:pathology; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects / Q000473:pathology; D014638:Vanadates / Q000493:pharmacokinetics / Q000633:toxicity*; D014639:Vanadium / Q000032:analysis / Q000378:metabolism; D014881:Water Supply
D009153:Mutagens; D014639:Vanadium; D014638:Vanadates; D004247:DNA