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A novel genotoxicity assay of carbon nanotubes using functional macrophage receptor with collagenous structure (MARCO)-expressing chicken B lymphocytes

  • Genotoxicity and Carcinogenicity
  • Published:
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Abstract

Although carbon nanotubes (CNTs) are promising nanomaterials, their potential carcinogenicity is a major concern. We previously established a genetic method of analyzing genotoxicity of chemical compounds, where we evaluated their cytotoxic effect on the DT40 lymphoid cell line comparing DNA-repair-deficient isogenic clones with parental wild-type cells. However, application of our DT40 system for the cytotoxic and genotoxic evaluation of nanomaterials seemed to be difficult, because DT40 cells only poorly internalized nanoparticles. To solve this problem, we have constructed a chimeric gene encoding a trans-membrane receptor consisting of the 5′ region of the transferrin receptor (TR) gene (to facilitate internalization of nanoparticles) and the 3′ region of the macrophage receptor with collagenous structure (MARCO) gene (which is a receptor for environmental particles). We expressed the resulting MARCO-TR chimeric receptor on DNA-repair-proficient wild-type cells and mutants deficient in base excision repair (FEN1 −/−) and translesion DNA synthesis (REV3 −/−). We demonstrated that the chimera mediates uptake of particles such as fluorescence-tagged polystyrene particles and multi-walled carbon nanotubes (MWCNTs), with very poor uptake of those particles by DT40 cells not expressing the chimera. MWCNTs were cytotoxic and this effect was greater in FEN1 −/−and REV3 −/− cells than in wild-type cells. Furthermore, MWCNTs induced greater oxidative damage (measured as 8-OH-dG formation) and a larger number of mitotic chromosomal aberrations in repair-deficient cells compared to repair-proficient cells. Taken together, our novel assay system using the chimeric receptor-expressing DT40 cells provides a sensitive method to screen for genotoxicity of CNTs and possibly other nanomaterials.

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References

  • Aisen P, Listowsky I (1980) Iron transport and storage proteins. Annu Rev Biochem 49:357–393

    Article  CAS  PubMed  Google Scholar 

  • Arredouani M, Yang Z, Ning Y, Qin G, Soininen R, Tryggvason K, Kobzik L (2004) The scavenger receptor MARCO is required for lung defense against pneumococcal pneumonia and inhaled particles. J Exp Med 200:267–272

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Buerstedde JM, Takeda S (1991) Increased ratio of targeted to random integration after transfection of chicken B cell lines. Cell 67:179–188

    Article  CAS  PubMed  Google Scholar 

  • Collawn JF, Lai A, Domingo D, Fitch M, Hatton S, Trowbridge IS (1993) YTRF is the conserved internalization signal of the transferrin receptor, and a second YTRF signal at position 31–34 enhances endocytosis. J Biol Chem 268:21686–21692

    CAS  PubMed  Google Scholar 

  • Cui D, Tian F, Ozkan CS, Wang M, Gao H (2005) Effect of single wall carbon nanotubes on human HEK293 cells. Toxicol Lett 155:73–85

    Article  CAS  PubMed  Google Scholar 

  • Dautry-Varsat A, Ciechanover A, Lodish HF (1983) pH and the recycling of transferrin during receptor-mediated endocytosis. Proc Natl Acad Sci USA 80:2258–2262

    Article  CAS  PubMed  Google Scholar 

  • Donaldson K, Tran CL (2002) Inflammation caused by particles and fibres. Inhal Toxicol 14:5–27

    Article  CAS  PubMed  Google Scholar 

  • Donaldson K, Aitken R, Tran L, Stone V, Duffin R, Forrest G, Alexander A (2006) Carbon nanotubes: a review of their properties in relation to pulmonary toxicology and workplace safety. Toxicol Sci 92:5–22

    Article  CAS  PubMed  Google Scholar 

  • Elomaa O, Kangas M, Sahlberg C, Tuukkanen J, Sormunen R, Liakka A, Thesleff I, Kraal G, Tryggvason K (1995) Cloning of a novel bacteria-binding receptor structurally related to scavenger receptors and expressed in a subset of macrophages. Cell 80:603–609

    Article  CAS  PubMed  Google Scholar 

  • Elomaa O, Sankala M, Pikkarainen T, Bergmann U, Tuuttila A, Raatikainen-Ahokas A, Sariola H, Tryggvason K (1998) Structure of the human macrophage MARCO receptor and characterization of its bacteria-binding region. J Biol Chem 273:4530–4538

    Article  CAS  PubMed  Google Scholar 

  • Evans TJ, Yamamoto KN, Hirota K, Takeda S (2010) Mutant cells defective in DNA repair pathways provide a sensitive high-throughput assay for genotoxicity. DNA Repair 9:1292–1298

    Article  CAS  PubMed  Google Scholar 

  • Gibbs PE, McDonald J, Woodgate R, Lawrence CW (2005) The relative roles in vivo of Saccharomyces cerevisiae Polη, Polζ, Rev1 protein and Pol32 in the bypass and mutation induction of an abasic site, T-T (6–4) photoadduct and T-T cis-syn cyclobutane dimer. Genetics 169:575–582

    Article  CAS  PubMed  Google Scholar 

  • Goldstein JL, Anderson RG, Brown MS (1979) Coated pits, coated vesicles, and receptor-mediated endocytosis. Nature 279:679–685

    Article  CAS  PubMed  Google Scholar 

  • Greaves DR, Gordon S (2005) Recent insights into the biology of macrophage scavenger receptors. J Lipid Res 46:11–20

    Article  CAS  PubMed  Google Scholar 

  • Hirano S, Kanno S, Furuyama A (2008) Multi-walled carbon nanotubes injure the plasma membrane of macrophages. Toxicol Appl Pharmacol 232:244–251

    Article  CAS  PubMed  Google Scholar 

  • Hirano S, Fujitani Y, Furuyama A, Kanno S (2010) Uptake and cytotoxic effects of multi-walled carbon nanotubes in human bronchial epithelial cells. Toxicol Appl Pharmacol 249:8–15

    Article  CAS  PubMed  Google Scholar 

  • Hirano S, Fujitani Y, Furuyama A, Kanno S (2012) Macrophage receptor with collagenous structure (MARCO) is a dynamic adhesive molecule that enhances uptake of carbon nanotubes by CHO-K1 cells. Toxicol Appl Pharmacol 259:96–103

    Article  CAS  PubMed  Google Scholar 

  • Hirota K, Sonoda E, Kawamoto T, Motegi A, Masutani C, Hanaoka F, Szuts D, Iwai S, Sale JE, Lehmann A, Takeda S (2010) Simultaneous disruption of two DNA polymerases, Polη and Polζ, in Avian DT40 cells unmasks the role of Polηin cellular response to various DNA lesions. PLoS Genet 6(10):e1001151

    Article  PubMed Central  PubMed  Google Scholar 

  • Hopkins CR, Trowbridge IS (1983) Internalization and processing of transferrin and the transferrin receptor in human carcinoma A431 cells. J Cell Biol 97:508–521

    Article  CAS  PubMed  Google Scholar 

  • Ji K, Kogame T, Choi K, Wang X, Lee JY, Taniguchi Y, Takeda S (2009) A novel approach using DNA repair-deficient chicken DT40 cell lines for screening and characterizing the genotoxicity of environmental contaminants. Environ Health Perspect 117:1737–1744

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ji K, Choi K, Giesy JP, Takeda S (2011a) Genotoxicity of several polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDEs, and their mechanisms of toxicity. Environ Sci Technol 45:5003–5008

    Article  CAS  PubMed  Google Scholar 

  • Ji K, Seo J, Liu X, Lee J, Lee S, Lee W, Park J, Khim JS, Hong S, Choi Y, Shim WJ, Takeda S, Giesy JP, Choi K (2011b) Genotoxicity and endocrine disruption potentials of sediment near an oil spill site: two years after the Hebei Spirit oil spill. Environ Sci Technol 45:7481–7488

    Article  CAS  PubMed  Google Scholar 

  • Jia G, Wang H, Yan L, Wang X, Pei R, Yan T, Zhao Y, Guo X (2005) Cytotoxicity of carbon nanomaterials: single-wall nanotube, multi-wall nanotube, and fullerene. Environ Sci Technol 39:1378–1383

    Article  CAS  PubMed  Google Scholar 

  • Jiang L, Nagai H, Ohara H, Hara S, Tachibana M, Hirano S, Shinohara Y, Kohyama N, Akatsuka S, Toyokuni S (2008) Characteristics and modifying factors of asbestos-induced oxidative DNA damage. Cancer Sci 99:2142–2151

    Article  CAS  PubMed  Google Scholar 

  • Kagan VE, Tyurina YY, Tyurin VA, Konduru NV, Potapovich AI, Osipov AN, Kisin ER, Schwegler-Berry D, Mercer R, Castranova V, Shvedova AA (2006) Direct and indirect effects of single walled carbon nanotubes on RAW 264.7 macrophages: role of iron. Toxicol Lett 165:88–100

    Article  CAS  PubMed  Google Scholar 

  • Kang S, Herzberg M, Rodrigues DF, Elimelech M (2008a) Antibacterial effects of carbon nanotubes: size does matter. Langmuir 24:6409–6413

    Article  CAS  PubMed  Google Scholar 

  • Kang S, Mauter MS, Elimelech M (2008b) Physicochemical determinants of multi-walled carbon nanotube bacterial cytotoxicity. Environ Sci Technol 42:7528–7534

    Article  CAS  PubMed  Google Scholar 

  • Kanno S, Furuyama A, Hirano S (2007) A murine scavenger receptor MARCO recognizes polystyrene nanoparticles. Toxicol Sci 97:398–406

    Article  CAS  PubMed  Google Scholar 

  • Karin M, Cao Y, Greten FR, Li ZW (2002) NF-kappa B in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2:301–310

    Article  CAS  PubMed  Google Scholar 

  • Kasai H, Nishimura S (1984) Hydroxylation of deoxyguanosine at the C-8 position by ascorbic acid and other reducing agents. Nucleic Acids Res 12:2137–2145

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kobzik L (1995) Lung macrophage uptake of unopsonized environmental particulates. Role of scavenger-type receptors. J Immunol 155:367–376

    CAS  Google Scholar 

  • Lam CW, James JT, McCluskey R, Hunter RL (2004) Pulmonary toxicity of single wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol Sci 77:126–134

    Article  CAS  PubMed  Google Scholar 

  • Lange SS, Takata K, Wood RD (2011) DNA polymerases and cancer. Nat Rev Cancer 11:96–110

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lindahl T, Wood RD (1999) Quality control by DNA repair. Science 286:1897–1905

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Lee J, Ji K, Takeda S, Choi K (2012) Potentials and mechanisms of genotoxicity of six pharmaceuticals frequently detected in fresh water environment. Toxicol Lett 211:70–76

    Article  CAS  PubMed  Google Scholar 

  • Lobrich M, Shibata A, Beucher A, Fisher A, Ensminger M, Goodarzi AA, Barton O, Jeggo PA (2010) γH2AX foci analysis for monitoring DNA double-strand break repair. Strengths, limitations and optimization. Cell Cycle 9:662–669

    Article  PubMed  Google Scholar 

  • Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto A, Naito M, Itakura H, Ikemoto S, Asaoka H, Hayakawa I, Kanamori H, Aburantani H, Tataku F, Suzuki H, Kobari Y, Miyai T, Takahashi K, Cohen EH, Wydro R, Houseman DE, Kodama T (1990) Human macrophage scavenger receptors: primary structure, expression and localization in atherosclerotic lesions. Proc Natl Acad Sci USA 87:9133–9137

    Article  CAS  PubMed  Google Scholar 

  • Matsuzaki Y, Adachi N, Koyama H (2002) Vertebrate cells lacking FEN1 endonuclease are viable but hypersensitive to methylating agents and H2O2. Nucleic Acid Res 30:3273–3277

    Article  CAS  PubMed  Google Scholar 

  • Monteiro-Riviere NA, Nemanich RJ, Inman AO, Wang YY, Riviere JE (2005) Multi-walled carbon nanotube interactions with human epidermal keratinocytes. Toxicol Lett 155:377–384

    Article  CAS  PubMed  Google Scholar 

  • Muller J, Decordier I, Hoet PH, Lombaert N, Thomassen L, Huaux F, Lison D, Kirsch-Volders M (2008) Clastogenic and aneugenic effects of multi-wall carbon nanotubes in epithelial cells. Carcinogenesis 29:427–433

    Article  CAS  PubMed  Google Scholar 

  • Murai J, Huang SY, Das BB, Renaud A, Zhang Y, Doroshow JH, Ji J, Takeda S, Pommier Y (2012) Trapping of PARP1 and PARP2 by clinical PARP inhibitors. Cancer Res 72:5588–5599

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Murakumo Y, Roth T, Ishii H, Rasio D, Numata S, Croce CM, Fishel R (2000) A human REV7 homolog that interacts with the polymerase zeta catalytic subunit hREV3 and the spindle assembly checkpoint protein hMAD2. J Biol Chem 275:4391–4397

    Article  CAS  PubMed  Google Scholar 

  • Nagai H, Okazaki Y, Chew SH, Misawa N, Yamashita Y, Akatsuka S, Ishihara T, Yamashita K, Yoshikawa Y, Yasui H, Jiang L, Ohara H, Takahashi T, Ichihara G, Kostarelos K, Miyata Y, Shinohara H, Toyokuni S (2011) Diameter and rigidity of multi-walled carbon nanotubes are critical factors in mesothelial injury and carcinogenesis. Proc Natl Acad Sci USA 108:1330–1338

    Article  Google Scholar 

  • Newman R, Schneider C, Sutherland R, Vodinelich L, Greaves M (1982) Trends Biochem Sci 7:397–400

    Article  CAS  Google Scholar 

  • Nojima K, Hochegger H, Saberi A, Fukushima T, Kikuchi K, Yoshimura M, Orelli BJ, Bishop DK, Hirano S, Ohzeki M, Ishiai M, Yamamoto K, Takata M, Arakawa H, Buerstedde JM, Yamazoe M, Kawamoto T, Araki K, Takahashi JA, Hashimoto N, Takeda S, Sonoda E (2005) Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells. Cancer Res 65:11704–11711

    Article  CAS  PubMed  Google Scholar 

  • Ock CY, Kim EH, Choi DJ, Lee HJ, Hahm KB, Chung MH (2012) 8-Hydroxydeoxyguanosine: not mere biomarker for oxidative stress, but remedy for oxidative stress-implicated gastrointestinal diseases. World J Gastroenterol 18:302–308

    Article  CAS  PubMed  Google Scholar 

  • Ohmori H, Friedberg EC, Fuchs RP, Goodman MF, Hanaoka F, Hinkle D, Kunkel TA, Lawrence CW, Livneh Z, Nohmi T, Prakash L, Prakash S, Todo T, Walker GC, Wang Z, Woodgate R (2001) The Y-family of DNA polymerases. Mol Cell 8:7–8

    Article  CAS  PubMed  Google Scholar 

  • Okada T, Sonoda E, Yoshimura M, Kawano Y, Saya H, Kohzaki M, Takeda S (2005) Multiple roles of vertebrate REV genes in DNA repair and recombination. Mol Cell Biol 25:6103–6111

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pacurari M, Yin XJ, Zhao J, Ding M, Leonard SS, Schwegler-Berry D, Ducatman BS, Sbarra D, Hoover MD, Castranova V, Vallyathan V (2008) Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappa B, and Akt in normal and malignant human mesothelial cells. Environ Health Perspect 116:1211–1217

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Palecanda A, Paulauskis J, Al-Mutairi E, Imrich A, Qin G, Suzuki H, Kodama T, Tryggvason K, Koziel H, Kobzik L (1999) Role of the scavenger receptor MARCO in alveolar macrophage binding of unopsonized environmental particles. J Exp Med 189:1497–1506

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Polk DB, Peek RM Jr (2010) Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer 10:403–414

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rogakou EP, Boon C, Redon C, Bonner WM (1999) Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol 146:905–916

    Article  CAS  PubMed  Google Scholar 

  • Shvedova AA, Castranova V, Kisin ER, Schwegler-Berry D, Murray AR, Gandelsman VZ, Maynard A, Baron P (2003) Exposure to carbon nanotube material: assessment of nanotube cytotoxicity using human keratinocyte cells. J Toxicol Environ Health A66:1909–1926

    Article  Google Scholar 

  • Shvedova AA, Kisin ER, Mercer R, Murray AR, Johnson VJ, Potapovich AI, Tyurina YY, Gorelik O, Arepalli S, Schwegler-Berry D, Hubbs AF, Antonini J, Evans DE, Ku BK, Ramsey D, Maynard A, Kagan VE, Castranova V, Baron P (2005) Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am J Physiol Lung Cell Mol Physiol 289:L698–L708

    Article  CAS  PubMed  Google Scholar 

  • Shvedova AA, Pietroiusti A, Fadeel B, Kagan VE (2012) Mechanisms of carbon nanotube-induced toxicity: focus on oxidative stress. Toxicol Appl Pharmacol 261:121–133

    Article  CAS  PubMed  Google Scholar 

  • Sonoda E, Sasaki SM, Buerstedde JM, Bezzubova O, Shinohara A, Ogawa H, Takata M, Yamaguchi-Iwai Y, Takeda S (1998) Rad51-deficient vertebrate cells accumulate chromosomal breaks prior to cell death. EMBO J 17:598–608

    Article  CAS  PubMed  Google Scholar 

  • Sonoda E, Okada T, Zhao GY, Tateishi S, Araki K, Yamaizumi M, Yagi T, Verkaik NS, van Gent DC, Takata M, Takeda S (2003) Multiple roles of Rev3, the catalytic subunit of pol zeta in maintaining genome stability in vertebrates. EMBO J 22:3188–3197

    Article  CAS  PubMed  Google Scholar 

  • Sutherland R, Delia D, Schneider C, Newman R, Kemshead J, Greaves M (1981) Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin. Proc Natl Acad Sci USA 78:4515–4519

    Article  CAS  PubMed  Google Scholar 

  • Takata M, Sasaki MS, Sonoda E, Morrison C, Hashimoto M, Utsumi H, Yamaguchi-Iwai Y, Shinohara A, Takeda S (1998) Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells. EMBO J 17:5497–5508

    Article  CAS  PubMed  Google Scholar 

  • Takata M, Sasaki MS, Tachiiri S, Fukushima T, Sonoda E, Schild D, Thompson LH, Takeda S (2001) Chromosome instability and defective recombinational repair in knockout mutants of the five Rad51 paralogs. Mol Cell Biol 21:2858–2866

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Thakur SA, Beamer CA, Migliaccio CT, Holian A (2009) Critical role of MARCO in crystalline silica-induced pulmonary inflammation. Toxicol Sci 108:462–471

    Article  CAS  PubMed  Google Scholar 

  • Tomlinson CG, Atack JM, Chapados BR, Tainer JA, Grasby JA (2010) Substrate recognition and catalysis by flap endonucleases and related enzymes. Biochem Soc Trans 38:433–437

    Article  CAS  PubMed  Google Scholar 

  • Van der Laan LJ, Dopp EA, Haworth R, Pikkarainen T, Kangas M, Elomaa O, Dijkstra CD, Gordon S, Tryggvason K, Kraal G (1999) Regulation and functional involvement of macrophage scavenger receptor MARCO in clearance of bacteria in vivo. J Immunol 162:939–947

    PubMed  Google Scholar 

  • Warheit DB, Laurence BR, Reed KL, Roach DH, Reynolds GA, Webb TR (2004) Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats. Toxicol Sci 77:117–125

    Article  CAS  PubMed  Google Scholar 

  • Wick P, Manser P, Limbach LK, Dettlaff-Weglikowska U, Krumeich F, Roth S, Stark WJ, Bruinink A (2007) The degree and kind of agglomeration affect carbon nanotube cytotoxicity. Toxicol Lett 168:121–131

    Article  CAS  PubMed  Google Scholar 

  • Wu X, Takenaka K, Sonoda E, Hochegger H, Kawanishi S, Kawamoto T, Takeda S, Yamazoe M (2006) Critical roles for polymerase zeta in cellular tolerance to nitric oxide-induced DNA damage. Cancer Res 66:748–754

    Article  CAS  PubMed  Google Scholar 

  • Yamazoe M, Sonoda E, Hochegger H, Takeda S (2004) Reverse genetic studies of the DNA damage response in the chicken B lymphocyte line DT40. DNA Repair 3:1175–1185

    Article  CAS  PubMed  Google Scholar 

  • Ye SF, Wu YH, Hou ZQ, Zhang QQ (2009) ROS and NF-kappa B are involved in upregulation of IL-8 in A549 cells exposed to multi-walled carbon nanotubes. Biochem Biophys Res Commun 379:643–648

    Article  CAS  PubMed  Google Scholar 

  • Yoshimura M, Kohzaki M, Nakamura J, Asagoshi K, Sonoda E, Hou E, Prasad R, Wilson SH, Tano K, Yasui A, Lan L, Seki M, Wood RD, Arakawa H, Buerstedde JM, Hochegger H, Okada T, Hiraoka M, Takeda S (2006) Vertebrate POLQ and POLbeta cooperate in base excision repair of oxidative DNA damage. Mol Cell 24:115–125

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

We thank the members of the S. T. laboratory and S. H. laboratory for help and support. This research was supported by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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There is no conflict of interest to declare.

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  1. Kouji Hirota

    Present address: Department of Chemistry, Tokyo Metropolitan University, 1-1 Minami-Ohsawa, Hachioji, Tokyo, 192-0397, Japan

Authors and Affiliations

  1. Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan

    Mohiuddin, Islam Shamima Keka, Terry John Evans, Kouji Hirota & Shunichi Takeda

  2. Department of Hygiene and Public Health, Graduate School of Medicine, Osaka Medical College, Osaka, 569-8686, Japan

    Mohiuddin, Hiroyasu Shimizu & Koichi Kono

  3. Environmental Nanotoxicology Section, RCER, National Institute for Environmental Studies, Tsukuba, Ibaraki, 305-8506, Japan

    Seishiro Hirano

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Correspondence to Shunichi Takeda or Seishiro Hirano.

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Mohiuddin, Keka, I.S., Evans, T.J. et al. A novel genotoxicity assay of carbon nanotubes using functional macrophage receptor with collagenous structure (MARCO)-expressing chicken B lymphocytes. Arch Toxicol 88, 145–160 (2014). https://doi.org/10.1007/s00204-013-1084-7

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