Aimed at the trivalent arsenic (As(III)) which is highly toxic and widely distributed in the environment, Prof. XU An and Prof. ZHAO Guoping’s joint group in Institute of Technical Biology and Agricultural Engineering, Hefei Institutes of Physical Science, managed to explain the combined genotoxicity of titanium dioxide nanoparticles (TiO₂ NPs ) and As(III).

Moreover, they also clarified the underlying mechanism by using the in vitro human-hamster hybrid (A_L) cells which are highly sensitive in detection of gene mutations.

As a typical representative of metal oxide nanomaterials, TiO₂ NPs are among the first metal oxide nanoparticles that were made commercially available to a wide variety of applications in materials, energy, electronics, biomedicine, environmental protection and other fields.

Due to their unique properties, such as a large surface area-to-volume ratio, high surface reactivity, and excellent affinity, TiO₂ NPs have shown great advantages in the application of pollutants' removal and detection, which may afford a good opportunity for TiO₂ NPs to interact with pollutants in the natural environment.

However, the interaction between TiO₂ NPs and pollutants in the environment remains unclear, the effects and the mechanisms of TiO₂ NPs on the fate, behavior, and bioavailability of pollutants are still need to be further studied.

In this study, the results 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 in the study had no cytotoxic or genotoxic effects on cells, they efficiently increased the genotoxicity of As(III) in 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 AL cells, this research discovered that mitochondria were essential for mediating the synergistic DNA-damaging effects of TiO₂ NPs and As(III).

This study provides novel mechanistic proof that TiO₂ NPs enhanced the genotoxicity of As(III) via physicochemical interactions, which were mediated by mitochondria dependent ROS.

The research also provides new experimental evidence and ideas for assessing the combined pollution risks of nanomaterials and other pollutants in the environment.

The above findings were published in journal Nanotoxicology titled "Amplification of arsenic genotoxicity by TiO₂ nanoparticles in mammalian cells: new insights from physicochemical interactions and mitochondria".

This work was supported in part by grants from National Program on Key Basic Research Project (973 Program), Strategic Leading Science & Technology Program (B), National Natural Science Foundation of China grants and The Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology, et al.

Schematic diagram illustrating the mechanism of the synergistic genotoxicity caused by TiO₂ NPs and As(III). (Image by WANG Xinan)