Synergistic genotoxicity caused by low concentration of titanium dioxide nanoparticles and p,p'-DDT in human hepatocytes.

The use of titanium dioxide nanoparticles (nano-TiO(2)) for the degradation of dichlorodiphenyltrichloroethane (p,p'-DDT) increases the risk of exposure to trace nano-TiO(2) and p,p'-DDT mixtures. The interaction of p,p'-DDT and nano-TiO(2) at low concentrations may alter toxic response relative to nano-TiO(2) or p,p'-DDT alone. In this work, the combined genotoxicity of trace nano-TiO(2) and p,p'-DDT on human embryo L-02 hepatocytes without photoactivation was studied. Nano-TiO(2) (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 mumol/L) and nano-TiO(2) (0, 0.01, 0.1, and 1 microg/mL) respectively. The adsorption of p,p'-DDT by nano-TiO(2) was approximately 0.3 mmol/g. Cell viability, apoptosis, and DNA double strand breaks were similar among all test groups. Nano-TiO(2) alone (0.01-1 microg/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-TiO(2) with trace p,p'-DDT synergistically enhanced genotoxicity via increasing oxidative stress, oxidative DNA adducts, DNA breaks, and chromosome damage in L-02 cells. Low concentrations of nano-TiO(2) and p,p'-DDT increased oxidativestress 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-TiO(2) suggests a potential environmental risk of nano-TiO(2) assisted photocatalysis. Copyright 2009 Wiley-Liss, Inc.