Amplification of arsenic genotoxicity by TiO₂ nanoparticles in mammalian cells: new insights from physicochemical interactions and mitochondria

Abstract

Titanium dioxide nanoparticles (TiO₂ NPs) have shown great adsorption capacity for arsenic (As); however, the potential impact of TiO₂ NPs on the behavior and toxic responses of As remains largely unexplored. In the present study, we focused on the physicochemical interaction between TiO₂ NPs and As(III) to clarify the underlying mechanisms involved in their synergistic genotoxic effect on mammalian cells. Our data showed that As(III) mainly interacted with TiO₂ NPs by competitively occupying the sites of hydroxyl groups on the surface of TiO₂ NP aggregates, resulting in more aggregation of TiO₂ NPs. Although TiO₂ NPs at concentrations used here had no cytotoxic or genotoxic effects on cells, they efficiently increased the genotoxicity of As(III) in human-hamster hybrid (A_L) cells. The synergistic genotoxicity of TiO₂ NPs and As(III) was partially inhibited by various endocytosis pathway inhibitors while it was completely blocked by an As(III)-specific chelator. Using a mitochondrial membrane potential fluorescence probe, a reactive oxygen species (ROS) probe together with mitochondrial DNA-depleted ρ⁰ A_L cells, we discovered that mitochondria were essential for mediating the synergistic DNA-damaging effects of TiO₂ NPs and As(III). These data provide novel mechanistic proof that TiO₂ NPs enhanced the genotoxicity of As(III) via physicochemical interactions, which were mediated by mitochondria-dependent ROS.

Keywords:

• TiO₂ nanoparticles (TiO₂ NPs)
• arsenic [As(III)]
• human–hamster hybrid (A_L) cells
• synergistic genotoxicity
• physicochemical interactions
• mitochondria

Acknowledgments

The authors thank Prof. Xingjiu Huang, Associate Prof. Zhen Jin for their supports in this work.

Disclosure statement

The authors declare no competing financial interest.

Additional information

Funding

This work was supported in part by grants from National Program on Key Basic Research Project (973 Program), 2014CB932002; Strategic Leading Science & Technology Program (B), XDB14030502; National Natural Science Foundation of China grants 21677147, 21507136 and 21607157; The Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology, 2014FXCX010; CASHIPS director's fund, YZJJ201501.