Oxidative damage and cell cycle delay induced by vanadium(III) in human peripheral blood 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 have shown 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 treated human peripheral blood lymphocytes in vitro, evaluated the effects of V2O3 on the phases of the cell cycle and the expression of molecules that control the cell cycle and examined DNA damage and the induction of oxidative stress. The results revealed that V2O3 did not affect cell viability at the different concentrations (2, 4, 8 or 16 μg/mL) or exposure times (24 h) used. However, V2O3 affected the percentage of G1- and S-phase cells in the cell cycle, decreased the expression of mRNAs encoding related proteins (cyclin D, cyclin E, CDK2 and CDK4) and increased the expression of γH2AX and the levels of reactive oxygen species. The ability of V2O3 to cause a cell cycle delay in G1-S phase may be associated with a decrease in the mRNA and protein expression of the cyclins/CDKs and with intracellular oxidative stress, which may cause DNA double-strand damage and H2AX phosphorylation.

Keywords

• Human lymphocytes
• Proteins
• MRNA
• Cyclins/CDKs
• γH2AX
• DNA damage