Keywords: 
• titanium dioxide nanoparticles /
• bisphenol A /
• physicochemical characters /
• combined exposure /
• DNA damage

Abstract: Titanium dioxide nanoparticles (nano-TiO₂) have been used widely and may react with a wide range of organic and biological molecules and then exhibit toxic effects in various cell lines, with or without photo activation. The effects of the interaction of TiO₂ nanoparticles (nano-TiO₂) with bisphenol A (BPA) on their physicochemical properties and DNA damage effects in human embryo L-02 hepatocytes were evaluated. Different concentrations of BPA (0, 0.1, 1, 10 μmol·L^-1) and nano-TiO₂ (0, 0.1, 1, 10 mg·L^-1) were mixed to analyze the size distribution, zeta potential and adsorption capacity of nano-TiO₂ in different media. Then L-02 cells were exposed to different concentration of BPA (0, 0.1, 1, 10 μmol·L^-1) and nano-TiO₂ (0, 0.1, 1, 10 mg·L^-1) for 24 hours, respectively. DNA damage and the expression of DNA repair enzymes O⁶-methylguanine-DNA methyltransferase (MGMT), DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and hMSH₂ in L-02 cells were analyzed. Results indicated that addition of BPA to nano-TiO₂ dispersions increased the aggregation level and zeta potential of nano-TiO₂ in all media. Nano-TiO₂ had a similar adsorption capacity in different media, although a higher aggregation level was observed in cell culture medium. Obviously, Interactions of nano-TiO₂ with BPA increased agglomeration and zeta potential, but did not influence the adsorption capacity of nano-TiO₂. The aggregated nano-TiO₂ can enrich BPA effectively. Toxicity analysis showed that nano-TiO₂ did not induce significant DNA damage, but the mixture ofnano-TiO₂ and BPA increased DNA double strand breaks and the expression of three DNA repair enzymes. It is clear that BPA and nano-TiO₂ mixture induce synergistic DNA damage effects. And hMSH₂, MGMT and DNA-PKcs all participated in the DNA damage repair pathway induced by the mixture of BPA and nano-TiO₂.