Biologia

Toxicology Letters 144 (2003) 359 Á/369 www.elsevier.com/locate/toxlet

Genotoxic effects of vanadium(IV) in human peripheral blood cells
Juan Jose Rodrıguez-Mercado, Elia Roldan-Reyes, Mario Altamirano´ ´ ´ Lozano *
Unidad de Investigacion en Genetica y Toxicologıa Ambiental (UNIGEN), Bioterio Campo-II, Facultad de Estudios Superiores´ ´ ´ Zaragoza, UNAM A.P. 9-020, Mexico 15000, D.F.,Mexico Received 10 March 2003; received in revised form 22 May 2003; accepted 22 May 2003

Abstract Vanadium has been considered an aneuploidogen; however, there is controversial information about the clastogenic effects of vanadium compounds. In this study, the genotoxicity of vanadium(IV) tetraoxide (V2O4) was evaluated in human cultured lymphocytes and leukocytes using the mitotic index (MI), thereplicative index (RI), chromosome aberrations (CA), sister chromatid exchanges (SCE), satellite associations (SA) and the single cell gel electrophoresis (SCGE) assay. This chemical induced a clear dose-response in MI inhibitions and modifications in the RI. In the CA, including breaks and exchanges and in the SCE, a significant increase appeared in the treated group compared with the controls.The SA test did not reveal an important difference. For the detection of genotoxic properties of vanadium(IV) using the SCGE assay, the 2 h evaluation period was not long enough for the chemical to enter the cell. These results indicate that vanadium(IV) tetraoxide is capable of inducing cytotoxic and cytostatic effects and chromosomal damage. # 2003 Elsevier Ireland Ltd. All rights reserved.Keywords: Structural chromosome aberration; Sister chromatid exchanges; Mitotic index; Replicative index; Single cell gel electrophoresis; Vanadium

1. Introduction In mammalian tissue, different metallic and organometallic compounds are transformed by metabolism, i.e. reduction/oxidation, alkylationdealkylation or conjugation processes; besides,
* Corresponding author. Tel.: '/52-5623-0706. E-mailaddress: maal@servidor.unam.mx (M. AltamiranoLozano).

results are often associated with changes in physicochemical properties and may significantly affect the nature and intensity of toxic effects (Manzo et al., 1992). Recent reviews have described the biochemical activity of vanadium, pointing out the importance of the redox reactions that this metal produces in the biological systems (Baran,1998, 2000). Vanadium has been recognized as an essential nutritional requirement in animals of a higher order,

0378-4274/03/$ - see front matter # 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S0378-4274(03)00255-8

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J.J. Rodrıguez-Mercado et al. / Toxicology Letters 144 (2003) 359 Á/369 ´

but its function is not clear; however, it is well established thatvanadium(V) and vanadium(IV) oxidation states may cause a number of adverse effects in mammals (Domingo, 1996; Aragon and ´ Altamirano-Lozano, 2001). The presence of vanadium(V) as a pollutant in the environment is mainly due to the combustion of oil and coal; furthermore, the available literature provides evidence that in mammalian systems vanadium(V) is biologically more active than vanadium(IV) ininducing toxic effects (Sabbioni et al., 1993). Vanadium(V) enters the cells through nonspecific anion channels and undergoes bio-reduction from vanadium(V) to vanadium(IV) (Heinz et al., 1982); vanadium may be reduced by cellular gluthatione, chatecols, cysteine, NADH, NADHP and L-ascorbic acid (Heinz et al., 1982; Sabbioni et al., 1993). Different types of tissue retain vanadium mainly as vanadium(IV)(Domingo, 1996). The data on the genotoxic and mutagenic potential of vanadium compounds in bacterial systems are inconclusive. Vanadium produces mitotic gene conversion in yeast; however, it presents no mutagenic effects in mammalian cells with and without microsomal S9 activation. Results found with vanadium in dominant lethal mutations are limited and inconclusive; still, some authors...