Metal nanoparticle-induced micronuclei and oxidative DNA damage in mice

Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Journal of Clinical Biochemistry and Nutrition (Impact Factor: 2.29). 05/2012; 50(3):211-6. DOI: 10.3164/jcbn.11-70
Source: PubMed

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, Fe(3)O(4), Fe(2)O(3), TiO(2), 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.

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    • "related DNA damage of CuONPs in experimental animals have been reported [19]. The fruit fly Drosophila melanogaster has been used to detect genotoxicity and mutagenicity of several metal and metal-oxide NPs [25] [26] [27] [28] [29] [30] [31]. "
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    ABSTRACT: Copper oxide nanoparticles (CuONPs) are used as semiconductors, catalysts, gas sensors, and antimicrobial agents. We have used the comet and wing-spot assays in Drosophila melanogaster to assess the genotoxicity of CuONPs and ionic copper (CuSO4). Lipid peroxidation analysis was also performed (Thiobarbituric Acid Assay, TBARS). In larval hemocytes, both CuONPs and CuSO4 caused significant dose-dependent increases in DNA damage (comet assay). In the wing-spot assay, an increase in the frequency of mutant spots was observed in the wings of the adults; CuONPs were more effective than was CuSO4. Both agents induced TBARS; again, CuONPs were more active than was CuSO4. The results indicate that CuONPs are genotoxic in Drosophila, and these effects may be mediated by oxidative stress. Most of the effects appear to be related to the presence of copper ions.
    Mutation Research/Genetic Toxicology and Environmental Mutagenesis 09/2015; 791:1-11. DOI:10.1016/j.mrgentox.2015.07.006 · 2.48 Impact Factor
    • "IONP, which is a complex mixture of silica-coated iron oxide nanoparticle functionalized with dithio group, showed these genotoxic/clastogenic effects for the first time in the fish A. anguilla L. To the author's knowledge , no study previously reported ENA frequency induction in fish under IONP in vitro conditions, which is one of the parameters recommended by OECD to evaluate the nanomaterial toxicity in a very short period of time (Arora et al. 2012). In addition, the maximum rate of ENA induction observed at 48 h of exposure in the current in vitro study aligns with the in vivo study done by Song et al. (2012), showing the maximum induction of micro-nucleated reticulocytes formation after 48 h in mice. Previously, a joint approach of micronuclei with other erythrocytic nuclear abnormalities has been reported in evaluating the genotoxicity of various classes of pollutants, including metal to different fish species (Ayllon and Garcia-Vazquez 2001; Guilherme et al. 2008; Mohmood et al. 2012). "
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    ABSTRACT: The study aimed to assess the genotoxic potential of silica-coated iron oxide nanoparticle functionalized with dithiocarbamate groups (IONP, 100 nm) in vitro exposure alone or its interference with mercury (Hg) co-exposure in the blood of European eel (Anguilla anguilla L.) by evaluating 8-hydroxy-2'-deoxyguanosine (8-OHdG), lipid peroxidation (LPO), and erythrocytic nuclear abnormalities (ENA). Four groups were made: (i) 2 × 10(6) erythrocytes + Roswell Park Memorial Institute-1640 (RPMI-1640) (control), (ii) 2 × 10(6) erythrocytes + IONP (2.5 mg L(-1)), (iii) 2 × 10(6) erythrocytes + Hg (50 μg L(-1)), and (iv) 2 × 10(6) erythrocytes + IONP + Hg. Blood plasma was also processed following the previous exposure conditions. Samplings were performed at 0, 2, 4, 8, 16, 24, 48, and 72 h of exposure. The results revealed significant ENA increases at both early (2, 4, 8) and late (16, 24, 48, 72) hours of exposure to IONP alone. However, IONP exposure combined with Hg co-exposure revealed no ENA increase at 2 h, suggesting that IONP-Hg complex formation is efficient to eliminate the DNA damage induced by individual exposure to IONP or Hg at early hours. Hence, the initial occurrence of antagonism between IONP and Hg was perceptible; however, at late hours of exposure, IONP was unable to mitigate the mercury-accrued negative impacts. Plasma exposure to IONP alone displayed a significant increase in 8-OHdG levels at 2 and 48 h of exposure. However, IONP in combination with Hg co-exposure revealed an increase in 8-OHdG levels at all the exposure length (except 16 h), suggesting that both IONP and Hg independently oxidized DNA. In addition, an additive effect on 8-OHdG levels at both early and late hours, and on LPO only at late hours (except 24 h), suggested that DNA is more susceptible to peroxidative damage than lipid.
    Environmental Science and Pollution Research 09/2014; 22(5). DOI:10.1007/s11356-014-3591-3 · 2.76 Impact Factor
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    • "Results on ROS production and induction of CAT activity were in agreement with previous reports on oxidative stress produced by different QDs in several in vitro sytems (Derfus et al., 2004; Kirchner et al., 2005; Ipe et al., 2005; Pujalté et al., 2011; Chen et al., 2012; Song et al., 2012). Both ROS production and CAT activity increased at lower Cd concentrations in ionic Cd exposure compared to both bulk and CdS QDs. "
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    ABSTRACT: CdS quantum dots (QDs) show a great promise for treatment and diagnosis of cancer and for targeted drug delivery, due to their size-tunable fluorescence and ease of functionalization for tissue targeting. In spite of their advantages it is important to determine if CdS QDs can exert toxicity on biological systems. In the present work, cytotoxicity of CdS QDs (5 nm) at a wide range of concentrations (0.001-100 mg Cd/L) was screened using neutral red (NR) and thiazolyl blue tetrazolium bromide (MTT) assays in isolated hemocytes and gill cells of mussels (Mytilus galloprovincialis). The mechanisms of action of CdS QDs were assessed at sublethal concentrations (0.31-5 mg Cd/L) in the same cell types through a series of functional in vitro assays: production of reactive oxygen species (ROS), catalase (CAT) activity, DNA damage, lysosomal acid phosphatase (AcP) activity, multixenobiotic resistance (MXR) transport activity, Na-K-ATPase activity (only in gill cells) and phagocytic activity and damage to actin cytoskeleton (only in hemocytes). Exposures to CdS QDs lasted for 24 h and were performed in parallel with exposures to bulk CdS and ionic Cd. Ionic Cd was the most toxic form to both cell types, followed by CdS QDs and bulk CdS. ROS production, DNA damage, AcP activity and MXR transport were significantly increased in both cell types exposed to the 3 forms of Cd. CAT activity increased in hemocytes exposed to the three forms of Cd while in gill cells only in those exposed to ionic Cd. No effects were found on hemocytes cytoskeleton integrity. Effects on phagocytosis were found in hemocytes exposed to bulk CdS and to CdS QDs at concentrations equal or higher than 1.25 mg Cd/L but not in those exposed to ionic Cd, indicating a particle-specific effect on phagocytosis. In conclusion, cell-mediated immunity and gill cell function represent significant targets for CdS QDs toxicity.
    Aquatic toxicology (Amsterdam, Netherlands) 08/2014; 153. DOI:10.1016/j.aquatox.2014.02.003 · 3.51 Impact Factor
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