Metal nanoparticle-induced micronuclei and oxidative DNA damage in mice

Abstract

Several mechanisms regarding the adverse health effects of nanomaterials have been proposed. Among them, oxidative stress is considered to be one of the most important. Many in vitro studies have shown that nanoparticles generate reactive oxygen species, deplete endogenous antioxidants, alter mitochondrial function and produce oxidative damage in DNA. 8-Hydroxy-2'-deoxyguanosine is a major type of oxidative DNA damage, and is often analyzed as a marker of oxidative stress in human and animal studies. In this study, we focused on the in vivo toxicity of metal oxide and silver nanoparticles. In particular, we analyzed the induction of micronucleated reticulocyte formation and oxidative stress in mice treated with nanoparticles (CuO, Fe3O4, Fe2O3, TiO2, Ag). For the micronucleus assay, peripheral blood was collected from the tail at 0, 24, 48 and 72 h after an i.p. injection of nanoparticles. Following the administration of nanoparticles by i.p. injection to mice, the urinary 8-hydroxy-2'-deoxyguanosine levels were analyzed by the HPLC-ECD method, to monitor the oxidative stress. The levels of 8-hydroxy-2'-deoxyguanosine in liver DNA were also measured. The results showed increases in the reticulocyte micronuclei formation in all nanoparticle-treated groups and in the urinary 8-hydroxy-2'-deoxyguanosine levels. The 8-hydroxy-2'-deoxyguanosine levels in the liver DNA of the CuO-treated group increased in a dose-dependent manner. In conclusion, the metal nanoparticles caused genotoxicity, and oxidative stress may be responsible for the toxicity of these metal nanoparticles.

Cytotoxicity and antibacterial activity of gold-supported cerium oxide nanoparticles

“…Cerium nitrate hexahydrate (Ce(NO 3 ) 3 ·6H 2 O, 99.9%, SigmaAldrich, St Louis, MO, USA), glycine (NH 2 ·CH 2 COOH, Fisher Scientific, Mumbai, India), chloroauric acid (HAuCl 4 , Loba Chemie, Mumbai, India), and sodium borohydride (NaBH 4 , Sigma-Aldrich) were used for synthesis of both CeO 2 and Au-impregnated CeO 2 nanoparticles.…”

Effects of copper oxide nanoparticles on developing zebrafish embryos and larvae

“…[3][4][5][6] In vivo studies also reported the potential genotoxic risk of CuO NPs, such as increased neoplastic lesions, point mutations, DNA alterations, and DNA strand breaks. 7,8 Some CuO NPs eventually enter the aquatic systems, raising concerns about toxicity from aqueous exposure.…”

Nanoparticles Toxicity and Their Routes of Exposures

“…Particularly the metal based NPs like Ag NPs [19], Au NPs [30] and TiO2 NPs [22] are important for that kind of ROS production and genetic damage. As a result of DNA damage induced by NPs, single-strand DNA breaks, doublestrand breaks, DNA deletions and genomic instability in the form of increase in 8-hydroxy-2-deoxyguanosine levels are formed [50]. According to Mroz et al [ 51] long-term exposure of cells to NPs displayed genome instability under comet assay analysis, altered cell cycle kinetics in flow cytometry and induced protein expression of p53, having a critical role in responding to various stresses that cause DNA damage, and DNA repair-related proteins.…”

“…Fen Song et al [50] analyzed the induction of reticulocyte micronuclei and oxidative DNA damage in ICR female mice after intraperitoneal injection of metal oxides (CuO, Fe2O3, Fe3O4, TiO2) and Ag NPs at various doses (0, 1, 3 mg/mouse). The results of the micronucleus assay demonstrated significant increases in micronucleated reticulocyte formation after the intraperitoneal administration of CuO, Fe2O3, Fe3O4, TiO2 and Ag NPs.…”