Synergistic Genotoxicity Caused by Low Concentration of Titanium Dioxide Nanoparticles and p,p '-DDT in Human Hepatocytes

The use of titanium dioxide nanoparticles (nano-TiO2) for the degradation of dichlorodiphenyltrichloroethane (p,p'-DDT) increases the risk of exposure to trace nano-TiO2 and p,p/-DDT mixtures. The interaction of p,p'-DDT and nano-TiO2 at low concentrations may alter toxic response relative to nano-TiO2 or p,p'-DDT alone. In this work, the combined genotoxicity of trace nano-TiO2 and p,p'-DDT on human embryo L-02 hepatocytes without photoactivation was studied. Nano-TiO2 (0.1 g/L) was mixed with 0.01-1 mmol/L p,p'-DDT to determine adsorption isotherms. L-02 cells were exposed to different levels of p,p'-DDT (0, 0.001, 0.01, and 0.1 mu mol/L) and nano-TiO2 (0, 0.01, 0.1, and 1 mu g/mL) respectively. The adsorption of p,p'-DDT by nano-TiO2 was approximately 0.3 mmol/g. Cell viability, apoptosis, and DNA double strand breaks were similar among all test groups. Nano-TiO2 alone (0.01-1 mu g/mL) increased the levels of oxidative stress and oxidative DNA adducts (8-OHdG), but it did not induce DNA breaks or chromosome damage. Addition of trace nano-TiO2 with trace p,p'-DDT synergistically enhanced genotoxiciiy via increasing oxidative stress, oxidative DNA adducts, DNA breaks, and chromosome damage in L-02 cells. Low concentrations of nano-TiO2 and p,p'-DDT increased oxidative stress by reactive oxygen species (ROS) formation and lipid oxidation. Oxidative stress is a major pathway for DNA and chromosome damage. Dose-dependent synergistic genotoxicity induced by combined exposure of trace p,p'-DDT and nano-TiO2 suggests a potential environmental risk of nano-TiO2 assisted photocatalysis. Environ. Mol. Mutagen. 51:192-204, 2010. (C) 2009 Wiley-Liss, Inc.