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 μmol/L) and nano‐TiO 2 (0, 0.01, 0.1, and 1 μg/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 μg/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. Environ. Mol. Mutagen., 2010. © 2009 Wiley‐Liss, Inc.