Coexposure to silver nanoparticles and ultraviolet A synergistically enhances the phosphorylation of histone H2AX.

Owing to the wide application of silver nanoparticles (AgNPs), the assessment of health risks associated with their use is of great importance. In this study, we revealed that the potential genotoxicity of AgNPs was enhanced by ultraviolet A (UVA) exposure. Three cultured cell lines were treated with AgNPs, followed by exposure to UVA. AgNPs induced phosphorylation of histone H2AX (γ-H2AX) following the formation of DNA double-strand breaks (DSBs), which was synergistically enhanced by UVA exposure. Enhanced γ-H2AX was observed only in cell lines that positively took up AgNPs, and microsized Ag particles, which were difficult to incorporate into cells, showed no γ-H2AX. Incorporation of AgNPs was not increased by UVA exposure. AgNO3 treatment followed by UVA exposure also induced a marked increase in γ-H2AX, indicating that the enhanced γ-H2AX was attributed to Ag ions released from AgNPs. Ag ions reacted with the -SH group of antioxidant molecules, such as glutathione, and induced intracellular oxidative conditions. 8-Hydroxy-2'-deoxyguanosine was formed in the cells treated with AgNPs, which was augmented by UVA irradiation, suggesting that intracellular oxidation caused oxidative DNA damage, leading to the enhanced formation of DSBs and γ-H2AX. Ag has been considered a safe metal; however, our results provide important insights into the influence of sunlight on the genotoxic potency of AgNPs.