Oxidative damage and cell cycle delay induced by vanadium(III) in human cells

Abstract

Vanadium (V) is a metal that can enter the environment through natural routes or anthropogenic activity. In the atmosphere, V is present as V oxides, among which vanadium(III) oxide (V2O3) stands out. Cytogenetic studies show that V2O3 is genotoxic and cytostatic and induces DNA damage; however, the molecular mechanisms leading to these effects have not been fully explored. Therefore, we used human peripheral blood lymphocytes treated in vitro and evaluated the effects of V2O3 on the phases of the cell cycle, the expression of molecules that control the cell cycle and detect DNA damage, and the induction of oxidative stress. The results reveal that V2O3 does not produce changes in cell viability at the concentrations (2, 4, 8 or 16 µg/mL) and exposure time (24 h) used. However, V2O3 modifies the percentage of G1 and S phase cells in the cell cycle, decreases the expression of mRNA in their respective proteins (cyclin D, cyclin E, cdk2 and cdk4) and increases the expression of γH2AX and the levels of reactive oxygen species. The ability of V2O3 to cause cell cycle delay in G1-S phase may be associated with a decrease in mRNA cyclin-cdk and its proteins and with intracellular oxidative stress, which may cause DNA double-strand damage and H2AX phosphorylation.