Genotoxicity and reactive oxygen species production induced by magnetite nanoparticles in mammalian cells

Kawanishi, Michihiro; Ogo, Sayaka; Ikemoto, Miho; Totsuka, Yukari; Ishino, Kousuke; Wakabayashi, Keiji; Yagi, Takashi

doi:10.2131/jts.38.503

Cited by 35 publications

(30 citation statements)

References 23 publications

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“…IONPs produce free radical species that reduce the levels of cellular antioxidants significantly, which may lead to apoptosis via oxidative damage to intracellular proteins, DNA and increased LPO (Belozerskaia and Gessler, 2007;Ahmad et al, 2010;Naziroglu et al, 2010;Wan et al, 2012). Previous studies by Konczol et al (2011) and Kawanishi et al (2013) have reported ROS generation in A549 and CHO cells treated with magnetite NPs. Current results showed a statistically significant decrease in the GSH content in comparison to control from 24 to 72 h in the IONP-treated cells.…”

Section: Discussionmentioning

confidence: 99%

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Iron oxide nanoparticles induced cytotoxicity, oxidative stress and DNA damage in lymphocytes

2017

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Over the past few decades nanotechnology and material science has progressed extremely rapidly. Iron oxide nanoparticles (IONPs) owing to their unique magnetic properties have a great potential for their biomedical and bioengineering applications. However, there is an inevitable need to address the issue of safety and health effects of these nanoparticles. Hence, the present study was aimed to assess the cytotoxic effects of IONPs on rats' lymphocytes. Using different assays, we studied diverse parameters including mitochondrial membrane potential, intracellular accumulation of reactive oxygen species (ROS), lactate dehydrogenase activity, antioxidant enzymes activity and DNA damage measurements. Intracellular metal uptake and ultrastructure analysis were also carried out through inductively coupled plasma atomic emission spectroscopy, transmission electron microscopy respectively. The results show that the IONP-induced oxidative stress was concentration-dependent in nature, with significant (P < 0.05) increase in ROS levels, lipid peroxidation level as well as depletion of antioxidant enzymes and glutathione. Moreover, we observed morphological changes in the cell after intracellular uptake and localization of nanoparticles in cells. From the findings of the study, it may be concluded that IONPs induce ROS-mediated cytotoxicity in lymphocytes. Copyright © 2017 John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 99%

“…Novotna et al () reported that ϒ Fe 2 O 3 increased oxidative stress and led to significant DNA damage. Kawanishi et al () found genotoxic effect of magnetite NPs in A549 and CHO cells. Karlsson et al () and Konczol et al () reported that Fe 2 O 3 and Fe 3 O 4 cause increased DNA migration detected by comet assay in the A549 cells.…”

Section: Discussionmentioning

confidence: 99%

Iron oxide nanoparticles induced cytotoxicity, oxidative stress and DNA damage in lymphocytes

2017

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“…The MN test was carried out as previously described (Kawanishi et al, 2013). Briefly, CHO cells (4 × 10 5 cells/dish) were seeded in φ60 mm plastic cell culture dishes one day before the infection procedure.…”

Section: Micronucleus Testmentioning

confidence: 99%

<i>In vitro</i> genotoxicity analyses of colibactin-producing <i>E. coli</i> isolated from a Japanese colorectal cancer patient

et al. 2019

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Colibactin is a polyketide-peptide genotoxin produced by enteric bacteria such as E. coli, and is considered to contribute to the development of colorectal cancer. We previously isolated E. coli strains from Japanese colorectal cancer patients, and in the present study we investigated the genotoxic potency of the colibactin-producing (clb +) E. coli strains that carry the polyketide synthases "pks" gene cluster (pks +) and an isogenic clbmutant in which the colibactin-producing ability is impaired. Measurement of phosphorylated histone H2AX indicated that DNA double strand breaks were induced in mammalian CHO AA8 cells infected with the clb + E. coli strains. Induction of DNA damage response (SOS response) by crude extract of the clb + strains was 1.7 times higher than that of the clb-E. coli in an umu assay with a Salmonella typhimurium TA1535/pSK1002 tester strain. Micronucleus test with CHO AA8 cells revealed that infection with the clb + strains induced genotoxicity, i.e., the frequencies of micronucleated cells infected with clb + strain were 4-6 times higher than with the clbstrain. Since the intestinal flora are affected by dietary habits that are strongly associated with ethnicity, these data may contribute to both risk evaluation and prevention of colorectal cancer in the Japanese population.

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“…Engineered nanomaterials (ENM) are used in various fields of the human environment, and assessment of their safety is, therefore, urgently required. So far, we have examined the genotoxicity of various ENM by using in vitro and in vivo assays, which indicated that inflammatory response, induced by macrophages and other immune cells, is considered a key mechanism for the genotoxicity and other toxic properties of ENM . In general, a single culture of tissue resident cells has been used for in vitro assays to evaluate genotoxicity of ENM.…”

Section: Introductionmentioning

confidence: 99%

Establishment of an in vivo simulating co‐culture assay platform for genotoxicity of multi‐walled carbon nanotubes

et al. 2018

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Engineered nanomaterials (ENM) are now used in a wide variety of fields, and, thus, their safety should urgently be assessed and secured. It has been suggested that inflammatory responses via the phagocytosis of ENM by macrophages is a key mechanism for their genotoxicity. The present study was conducted to establish a mechanism‐based assay to evaluate the genotoxicity of ENM under conditions simulating an in vivo situation, featuring a co‐culture system of murine lung resident cells (GDL1) and immune cells (RAW264.7). GDL1 were cultured with or without RAW264.7, exposed to a multi‐walled carbon nanotube (MWCNT), and then analyzed for mutagenicity and underlying mechanisms. Mutation frequencies induced in GDL1 by the MWCNT were significantly greater with the co‐existence of RAW264.7 than in its absence. Mutation spectra observed in GDL1 co‐cultured with RAW264.7 were different from those seen in GDL1 cultured alone, but similar to those observed in the lungs of mice exposed to the MWCNT in vivo. Inflammatory cytokines, such as IL‐1β and TNF‐α, were produced from RAW264.7 cells treated with the MWCNT. The generation of reactive oxygen species and the formation of 8‐oxodeoxyguanosine in GDL1 exposed to the MWCNT were greater in the co‐culture conditions than in the single culture conditions. Based on these findings, it is indicated that inflammatory responses are involved in the genotoxicity of MWCNT, and that the presently established, novel in vitro assay featuring a co‐culture system of tissue resident cells with immune cells is suitable to evaluate the genotoxicity of ENM.

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Genotoxicity and reactive oxygen species production induced by magnetite nanoparticles in mammalian cells

Cited by 35 publications

References 23 publications

Iron oxide nanoparticles induced cytotoxicity, oxidative stress and DNA damage in lymphocytes

Iron oxide nanoparticles induced cytotoxicity, oxidative stress and DNA damage in lymphocytes

<i>In vitro</i> genotoxicity analyses of colibactin-producing <i>E. coli</i> isolated from a Japanese colorectal cancer patient

Establishment of an in vivo simulating co‐culture assay platform for genotoxicity of multi‐walled carbon nanotubes

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