Madoka Nakajima

Publications (32) View all

• Article: In vivo comet assay of multi-walled carbon nanotubes using lung cells of rats intratracheally instilled.

  Makoto Ema, Shoji Masumori, Norihiro Kobayashi, Masato Naya, Shigehisa Endoh, Junko Maru, Masayo Hosoi, Fuyumi Uno, Madoka Nakajima, Makoto Hayashi, Junko Nakanishi
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  ABSTRACT: The genotoxicity of multi-walled carbon nanotubes (MWCNTs) was evaluated in vivo with comet assays using the lung cells of rats given MWCNTs. The MWCNTs were intratracheally instilled as a single dose at 0.2 or 1.0 mg kg(-1) or a repeated dose at 0.04 or 0.2 mg kg(-1) , once a week for 5 weeks, to male rats. The rats were sacrificed 3 or 24 h after the single instillation and were sacrificed 3 h after the last instillation in the repeated instillation groups. Histopathological examinations of the lungs revealed that MWCNTs caused inflammatory changes including the infiltration of macrophages and neutrophils after a single instillation and repeated instillation at both doses. In comet assays using rat lung cells, no changes in % Tail DNA were found in any group given MWCNTs. These findings indicate that MWCNTs do not have the potential to cause DNA damage in comet assays using the lung cells of rats given MWCNTs at doses causing inflammatory responses. Copyright © 2012 John Wiley & Sons, Ltd.
  Journal of Applied Toxicology 08/2012; · 2.48 Impact Factor
• Article: In vivo genotoxicity study of single-wall carbon nanotubes using comet assay following intratracheal instillation in rats.

  Masato Naya, Norihiro Kobayashi, Shigehisa Endoh, Junko Maru, Kazumasa Honda, Makoto Ema, Jin Tanaka, Masahito Fukumuro, Kazushige Hasegawa, Madoka Nakajima, Makoto Hayashi, Junko Nakanishi
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  ABSTRACT: The genotoxicity of single-wall carbon nanotubes (SWCNTs) was evaluated in vivo using the comet assay after intratracheal instillation in rats. The SWCNTs were instilled at a dosage of 0.2 or 1.0mg/kg body weight (single instillation group) and 0.04 or 0.2mg/kg body weight once a week for 5weeks (repeated instillation group). As a negative control, 1% Tween 80 was instilled in a similar manner. As a positive control, ethyl methanesulfonate (EMS) at 500mg/kg was administered once orally 3h prior to dissection. Histopathologically, inflammation in the lung was observed for all the SWCNTs in both single and repeated groups. In the comet assay, there was no increase in% tail DNA in any of the SWCNT-treated groups. In the EMS-treated groups, there was a significant increase in% tail DNA compared with the negative control group. The present study indicated that a single intratracheal instillation of SWCNTs (1.0mg/kg) or repeated intratracheal instillation (0.2mg/kg) once a week for five weeks induced a clear inflammatory response (hemorrhage in the alveolus, infiltration of alveolar macrophages and neutrophiles), but no DNA damage, in the lungs in rats. Under the conditions of the test, SWCNTs were not genotoxic in the comet assay following intratracheal instillation in rats.
  Regulatory Toxicology and Pharmacology 06/2012; 64(1):124-9. · 2.43 Impact Factor
• Article: Discrimination of genotoxic and non-genotoxic hepatocarcinogens by statistical analysis based on gene expression profiling in the mouse liver as determined by quantitative real-time PCR.

  Takashi Watanabe, Takayoshi Suzuki, Masakatsu Natsume, Madoka Nakajima, Kazunori Narumi, Shuichi Hamada, Tomohiro Sakuma, Akiko Koeda, Keiyu Oshida, Yohei Miyamoto, [......], Wakako Ohyama, Emiko Okada, Yohei Fujiishi, Shizuyo Sutou, Ayami Tadakuma, Yasuyoshi Ishikawa, Mahoko Kido, Rina Minamiguchi, Izumi Hanahara, Chie Furihata
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  ABSTRACT: The general aim of the present study is to discriminate between mouse genotoxic and non-genotoxic hepatocarcinogens via selected gene expression patterns in the liver as analyzed by quantitative real-time PCR (qPCR) and statistical analysis. qPCR was conducted on liver samples from groups of 5 male, 9-week-old B6C3F(1) mice, at 4 and 48h following a single intraperitoneal administration of chemicals. We quantified 35 genes selected from our previous DNA microarray studies using 12 different chemicals: 8 genotoxic hepatocarcinogens (2-acetylaminofluorene, 2,4-diaminotoluene, diisopropanolnitrosamine, 4-dimethylaminoazobenzene, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, N-nitrosomorpholine, quinoline and urethane) and 4 non-genotoxic hepatocarcinogens (1,4-dichlorobenzene, dichlorodiphenyltrichloroethane, di(2-ethylhexyl)phthalate and furan). A considerable number of genes exhibited significant changes in their gene expression ratios (experimental group/control group) analyzed statistically by the Dunnett's test and Welch's t-test. Finally, we distinguished between the genotoxic and non-genotoxic hepatocarcinogens by statistical analysis using principal component analysis (PCA) of the gene expression profiles for 7 genes (Btg2, Ccnf, Ccng1, Lpr1, Mbd1, Phlda3 and Tubb2c) at 4h and for 12 genes (Aen, Bax, Btg2, Ccnf, Ccng1, Cdkn1a, Gdf15, Lrp1, Mbd1, Phlda3, Plk2 and Tubb2c) at 48h. Seven major biological processes were extracted from the gene ontology analysis: apoptosis, the cell cycle, cell proliferation, DNA damage, DNA repair, oncogenes and tumor suppression. The major, biologically relevant gene pathway suggested was the DNA damage response pathway, resulting from signal transduction by a p53-class mediator leading to the induction of apoptosis. Eight genes (Aen, Bax, Btg2, Ccng1, Cdkn1a, Gdf15, Phlda3 and Plk2) that are directly associated with Trp53 contributed to the PCA. The current findings demonstrate a successful discrimination between genotoxic and non-genotoxic hepatocarcinogens, using qPCR and PCA, on 12 genes associated with a Trp53-mediated signaling pathway for DNA damage response at 4 and 48 h after a single administration of chemicals.
  Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 05/2012; 747(2):164-75. · 2.85 Impact Factor
• Article: Genotoxicity evaluation of fullerene C60 nanoparticles in a comet assay using lung cells of intratracheally instilled rats.

  Makoto Ema, Jin Tanaka, Norihiro Kobayashi, Masato Naya, Shigehisa Endoh, Junko Maru, Masayo Hosoi, Miho Nagai, Madoka Nakajima, Makoto Hayashi, Junko Nakanishi
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  ABSTRACT: The genotoxicity of fullerene C(60) nanoparticles was evaluated in vivo with comet assays using the lung cells of rats given C(60) nanoparticles. The C(60) nanoparticles were intratracheally instilled as a single dose at 0.5 or 2.5mg/kg or repeated dose at 0.1 or 0.5mg/kg, once a week for 5 weeks, to male rats. The lungs were obtained 3 or 24h after a single instillation and 3h after repeated instillation. Inflammatory responses were observed in the lungs obtained 24h after a single instillation at 2.5mg/kg and repeated instillation at 0.5mg/kg. Histopathological examinations revealed that C(60) nanoparticles caused slight changes including hemorrhages in alveoli and the cellular infiltration of macrophages and neutrophils in alveoli. In comet assays using rat lung cells, no increase in % Tail DNA was found in any group given C(60) nanoparticles. These findings indicate that C(60) nanoparticles had no potential for DNA damage in comet assays using the lungs cells of rats given C(60) even at doses causing inflammation.
  Regulatory Toxicology and Pharmacology 01/2012; 62(3):419-24. · 2.43 Impact Factor
• Article: Differences in micronucleus induction in peripheral blood reticulocytes of mice exposed to N-ethyl-N-nitrosourea at light and dark dosing times.

  Keiichi Itoh, Shoji Masumori, Madoka Nakajima, Makoto Hayashi, Hiroyuki Sakakibara, Kayoko Shimoi
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  ABSTRACT: Mammals, including human beings, have a circadian clock system to regulate behavioral and physiological processes. In this study, we investigated the effect of dosing time on micronucleus induction in the bone marrow by evaluating the frequencies of micronucleated peripheral reticulocytes (MNRETs) in mice exposed to N-ethyl-N-nitrosourea (ENU) to assess any difference in genotoxic sensitivity to chemicals between light and dark periods (inactive phase for rodents and active phase for rodents). Male C3H/He mice were treated intraperitoneally with ENU (12.5 or 25 mg/kg body weight) at zeitgeber time (ZT) 3 in the light period or ZT15 in the dark period, and then the time courses of the frequencies of the MNRETs were determined. The frequencies of the MNRETs induced by ENU increased time-dependently and peaked at 48 hr after treatment for ZT3 and ZT15, and were obviously higher in the ZT15 treatment group than the ZT3 treatment group. The MNRETs were measured at 48 hr after treatment with ENU (25 mg/kg body weight) at various dosing times (ZT0, 3, 6, 12, 15 and 18). The frequencies of the MNRETs in mice treated at ZT0, 15 and 18 were significantly higher than those in mice treated at ZT3, 6 and 12. These results suggest that genotoxic sensitivity to chemicals in mouse bone marrow is different between light and dark periods maybe due to different biological responses (detoxification, cell cycle, DNA repair, etc.) related to circadian rhythms.
  The Journal of Toxicological Sciences 01/2012; 37(2):427-30. · 1.52 Impact Factor