title: Synergistic genotoxicity caused by low concentration of titanium dioxide nanoparticles and p,p'-DDT in human hepatocytes.
abstract: 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.
authors.affiliation: MOE Key Laboratory of Environment & Health, Institute of Environmental Medicine, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.forename: Jiang-Hua
authors.initials: JH
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Jiang
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Zhu
authors.forename: He-Qing
authors.initials: HQ
authors.lastname: Tan
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000327:Adsorption / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003634:DDT / Q000737:chemistry / Q000633:toxicity*; D053960:DNA Breaks; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D014025:Titanium / Q000737:chemistry / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D009153:Mutagens; C009495:titanium dioxide; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003634:DDT; D014025:Titanium; D003849:Deoxyguanosine