Evaluation of genotoxicity of oral exposure to tetravalent vanadium in vivo

Section of Toxicology and Biomedical Sciences, ENEA-CR Casaccia, Rome, Italy.
Toxicology Letters (Impact Factor: 3.26). 05/2007; 170(1):11-8. DOI: 10.1016/j.toxlet.2006.07.343
Source: PubMed


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.

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    • ") reported DNA single-strand breaks in kidney, liver and lung cells but not in BM. Villani et al. (2007) evaluated the genotoxic potential (micronucleus and DNA damage) of tetravalent vanadium (VOSO 4 ) administered orally in CD1 mice. The authors reported no increase in the frequency of micronucleated peripheral reticulocytes or BM cells, similarly no DNA damage was observed in testicular or BM cells. "
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    ABSTRACT: Vanadium is an environmental pollutant attached to the smallest air suspended particles that enters into the respiratory tract reaching the systemic circulation. The oxidative state of this element and sex are factors related to its toxicity. In this study, we explored sex-associated genotoxic and cytotoxic differences in a mouse experimental model. Mice inhaled V2 O5 (0.02 M) 2 h/twice a week; blood samples were obtained at 24 h and every week until the end of the 4-week exposure. Samples were processed for fluorochrome-mediated viability and a micronucleus assay in slides pre-covered with acridine orange (AO). The results showed that males were more susceptible to genotoxicity during the exposure in contrast to the females. In peripheral blood leukocytes, no cytotoxic differences were observed in both, females or males, but the decrease in circulating reticulocytes provides evidence of the metal's cytotoxic effect on the bone marrow (BM). A significant decrease in reticulocytes was observed during the experiment independent of the animal's sex. The present findings might be explained by the interaction of the metal with the enzymes that control erythropoiesis or a direct effect on erythropoietin production might explain our findings; however, an absence of the genotoxic effects in females could be a consequence of the protective effect against oxidative stress by their higher estrogen levels. This study contributes to a better understanding of the mechanisms by which vanadium induces adverse effects in biological systems. Copyright © 2013 John Wiley & Sons, Ltd.
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    • "The results revealed no significant damage in the germ cells, indicating that oral exposure to vanadium is not genotoxic in these cells; however, damage was observed in the somatic cells only at the highest doses, possibly because of the low bioavailability of vanadium in these cells (Leopardi et al., 2005). Villani et al. (2007) evaluated the effects of oral administration of VOSO 4 on male CD-1 mice at doses of 10, 100, 500, or 1000 mg/L for 5 weeks, using the Comet assay and MN test, which yielded no treatment-related changes; thus, this metal (as V[IV]) was not genotoxic in somatic and germ cells. However, given the various biological effects on cellular mechanisms, the authors recommend caution in applying these results to the evaluation of other vanadium compounds. "
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    ABSTRACT: Abstract Research on the biological effects of vanadium in humans has shown that acute poisoning in workers can manifest itself in a number of symptoms. There are no reports in humans about reproductive and developmental effects induced by vanadium compounds in humans; however, some studies with rats and mice indicate that vanadium can cross the placental barrier and accumulate in fetal membranes rather than the fetus itself. In this case, probably most consequences of administration of vanadium to pregnant females like reabsorptions, fetal death and reduction in size can be the result of maternal toxicity. Concerning genetic and related effects in humans exposed to different vanadium compounds, data are controversial. Data on genotoxic effects in workers exposed to vanadium indicate that they can have an increased risk to develop cancer, and DNA instability can give rise to an onset of genetic syndromes, fetal malformations, and cancer. This paper presents materials presented at the 8th International Symposium on Vanadium Chemistry, Biological Chemistry, and Toxicology in a session titled 'Relationship between occupational and environmental exposure to vanadium compounds and the reprotoxic and genotoxic effects'.
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    • "No financial interest is declared. The authors were co-authors of two of the publications quoted[33,34] "
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    ABSTRACT: Metal contaminants in drinking water represent a relevant health issue in several areas of the world. In Italy, because of the geological features of the territory, high arsenic and vanadium are frequently reported in ground waters in concentrations above current guideline values. The implications for public health of the presence of contaminants above their legal limit are directly related to the biological basis of the guideline value. In the case of arsenic there are still major uncertainties in the mechanism of carcinogenesis which prevent a precise evaluation of long-term risks. Thus, the guideline value endorsed in the European Community (10 micro;g/L) has to be considered as a pragmatic tool rather than a quality objective, bearing in mind that "every effort should be made to keep concentrations as low as reasonably possible" (WHO, 2011). A reverse situation holds for vanadium, for which a strict national limit (50 micro;g/L) was previously proposed in consideration of data gaps, and for which new evidence indicated a less stringent health-based limit.
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