Evaluation of genotoxicity of oral exposure to tetravalent vanadium in vivo.
The trace element vanadium interacts with living cells, in which it exerts a variety of biological effects depending on its chemical form and oxidation state. Tetravalent vanadium was shown to affect several genotoxicity end-points in vitro, but its genotoxic potential in vivo is not elucidated. In this study, the genotoxic effects induced in vivo by subacute oral exposure to vanadyl sulphate (VOSO4), a tetravalent vanadium salt, were investigated. To this aim male CD1 mice were administered with VOSO4 in drinking water over the dose range 2-1000 mg/l for 5 weeks. The incidence of micronucleated blood reticulocytes was measured along treatment period. At the end of treatment, micronuclei in both blood reticulocytes and bone marrow polychromatic erythrocytes were determined; in addition, DNA lesions detectable by comet assay were assessed in marrow and testicular cells. Tissue distribution of vanadium at sacrifice was determined by atomic absorption spectrometry. Comet assays and the analysis of micronuclei in polychromatic erythrocytes did not reveal treatment related effects. A slight increase in micronucleated reticulocytes, with no relationship with the administered dose, was observed in some treated groups. The determination of vanadium content in kidney, liver, spleen, bone, stomach, small intestine and testis highlighted low internal exposure, especially in soft tissues. Overall, data indicate scarce bioavailability for orally administered tetravalent vanadium, and lack of significant genotoxic potential in vivo.
Villani
Paola
P
Section of Toxicology and Biomedical Sciences, ENEA-CR Casaccia, Rome, Italy.
Cordelli
Eugenia
E
Leopardi
Paola
P
Siniscalchi
Ester
E
Veschetti
Enrico
E
Fresegna
Anna Maria
AM
Crebelli
Riccardo
R
D000284:Administration, Oral; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D020552:Comet Assay; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D009153:Mutagens / Q000493:pharmacokinetics / Q000633:toxicity*; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D017968:Vanadium Compounds / Q000493:pharmacokinetics / Q000633:toxicity*
D009153:Mutagens; D017968:Vanadium Compounds; C034028:vanadyl sulfate