Aspect ratio has no effect on genotoxicity of multi-wall carbon nanotubes
Tóm tắt
Carbon nanotubes (CNTs) have specific physico-chemical and electrical properties that are useful for telecommunications, medicine, materials, manufacturing processes and the environmental and energy sectors. Yet, despite their many advantages, it is also important to determine whether CNTs may represent a hazard to the environment and human health. Like asbestos, the aspect ratio (length:diameter) and metal components of CNTs are known to have an effect on the toxicity of carbon nanotubes. Thus, to evaluate the toxic potential of CNTs in relation to their aspect ratio and metal contamination, in vivo and in vitro genotoxicity tests were conducted using high-aspect-ratio (diameter: 10–15 nm, length: ~10 μm) and low-aspect-ratio multi-wall carbon nanotubes (MWCNTs, diameter: 10–15 nm, length: ~150 nm) according to OECD test guidelines 471 (bacterial reverse mutation test), 473 (in vitro chromosome aberration test), and 474 (in vivo micronuclei test) with a good laboratory practice system. To determine the treatment concentration for all the tests, a solubility and dispersive test was performed, and a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) solution found to be more suitable than distilled water. Neither the high- nor the low-aspect-ratio MWCNTs induced any genotoxicity in a bacterial reverse mutation test (~1,000 μg/plate), in vitro chromosome aberration test (without S9: ~6.25 μg/ml, with S9: ~50 μg/ml), or in vivo micronuclei test (~50 mg/kg). However, the high-aspect-ratio MWCNTs were found to be more toxic than the low-aspect-ratio MWCNTs. Thus, while high-aspect-ratio MWCNTs do not induce direct genotoxicity or metabolic activation–mediated genotoxicity, genotoxicity could still be induced indirectly through oxidative stress or inflammation.
Tài liệu tham khảo
Aillon KL, Xie Y, El-Gendy N, Berkland CJ, Forrest ML (2009) Effects of nanomaterial physicochemical properties on in vivo toxicity. Adv Drμg Deliv Rev 61:457–466
Aubin-Tam ME, Hamad-schifferli K (2008) Structure and function of nanoparticle-protein conjugates. Biomed Mater 3:1–17
Bianco A, Kostarelos K, Partidos CD, Prato M (2005) Biomedical applications of functionalised carbon nanotubes. Chem Commun 5:571–577
Bonnemann H, Richards RM (2001) Nanoscopic metal particles-synthetic methods and potential applications. Eur J Inorg Chem 10:2455–2480
Bottini M, Tautz L, Huynh H, Monosov E, Bottini N, Bellucci S, Mustelin T (2005) Covalent decoration of multiwalled carbon nanotubes with silica nanoparticles. Chem Commun 6:758–760
Bottini M, Bruckner S, Nika K, Bottini N, Bellucci S, Magrini A, Bergamaschi A, Mustelin T (2006) Multi-walled carbon nanotubes induce T lymphocyte apoptosis. Toxicol Lett 160:121–126
Braydich-Stolle L, Hussain S, Schlager JJ, Hofmann MC (2005) In vitro cytotoxicity of nanoparticles in mammalian germline stem cells. Toxicol Sci 88:412–419
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
Di Sotto A, Chiaretti M, Carru GA, Bellucci S, Mazzanti G (2009) Multi-walled carbon nanotubes: lack of mutagenic activity in the bacterial reverse mutation assay. Toxicol Lett 184:192–197
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
Gooding JJ, Wibowon R, Liu JQ, Yang WR, Losic D, Orbons S, Mearns FJ, Shapter JG, Hibbert DB (2003) Protein electrochemistry using aligned carbon nanotube arrays. J Am Chem Soc 125:9006–9007
Helland A, Wick P, Koehler A, Schmid K, Som C (2007) Reviewing the environmental and human health knowledge base of carbon nanotubes. Environ Health Perspect 115:1125–1131
Hu H, Ni YC, Montana V, Haddon RC, Parpura V (2004) Chemically functionalized carbon nanotubes as substrates for neuronal growth. Nano Lett 4:507–511
Hussain SM, Hess KL, Gearhart JM, Geiss KT, Schlager JJ (2005) In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol In Vitro 19:975–983
IARC (1977) Monographs on the evaluation of carcinogenic risk to chemicals on man: Asbestos. 14:1–106
Kam NWS, Liu Z, Dai HJ (2005) Functionalization of carbon nanotubes via cleavable disulfide bonds for efficient intracellular delivery of siRNA and potent gene silencing. J Am Chem Soc 127:12492–12493
Korean Agency for Technology and Standards (2009) Korean Industrial Standards D 2717, Evaluation method for the degree of macrodispersion of carbon nanotubes using UV-VIS-NIR absorption spectroscopy
Lee JY, Kim JS, An KH, Lee K, Kim DY, Bae DJ, Lee YH (2005) Electrophoretic and dynamic light scattering in evaluating dispersion and size distribution of single-walled carbon nanotubes. J Nanosci Nanotechnol 5:1045–1049
Lewinski N, Colvin V, Drezek R (2008) Cytotoxicity of nanoparticles. Small 4:26–49
Lin Y, Taylor S, Li H, Fernando SKA, Qu L, Wang W, Gu L, Zhou B, Sun YP (2004) Advances towards bioapplications of carbon nanotubes. J Mater Chem 14:527–541
Lindberg HK, Falck GC, Suhonen S, Vippola M, Vanhala E, Catalán J, Savolainen K, Norppa H (2009) Genotoxicity of nanomaterials: DNA damage and micronuclei induced by carbon nanotubes and graphite nanofibres in human bronchial epithelial cells in vitro. Toxicol Lett 186:166–173
Liu Z, Sun XM, Nakayama-Ratchford N, Dai HJ (2007a) Supramolecular chemistry on water-soluble carbon nanotubes for drug loading and delivery. ACS Nano 1:50–56
Liu Z, Winters M, Holodniy M, Dai HJ (2007b) SiRNA delivery into human T cells and primary cells with carbon-nanotube transporters. Angew Chem Int Ed 46:2023–2027
MacGregor JT, Heddle JA, Hite M, Margolin BH, Ramel C, Salamone MF, Tice RR, Wild D (1987) Guidelines for the conduct of micronucleus assays in mammalian bone marrow erythrocytes. Mutat Res 189:103–112
Maron DM, Ames BN (1983) Reviewed methods for the Salmonella mutagenicity test. Mutat Res 113:173–215
Mattson MP, Haddon RC, Rao AM (2000) Molecular functionalization of carbon nanotubes and use as substrates for neuronal growth. J Mol Neurosci 14:175–182
Medina C, Santos-Martinez MJ, Radomski A, Corrigan OI, Radomski MW (2007) Nanoparticles: pharmacological and toxicological significance. Br J Pharmacol 150:552–558
Murphy CJ (2002) Materials science: nanocubes and nanoboxes. Science 298:2139–2141
OECD (Organization for Economic Cooperation and Development) (1997) OECD Guideline 471, bacterial reverse mutation test, OECD Guidelines for Testing of Chemicals, OECD, Paris, France
OECD (Organization for Economic Cooperation and Development) (1997) OECD Guideline 473, In vitro mammalian chromosome aberration test, OECD Guidelines for Testing of Chemicals, OECD, Paris, France
OECD (Organization for Economic Cooperation and Development) (1997) OECD Guideline 474, Mammalian erythrocyte micronucleus test, OECD Guidelines for Testing of Chemicals, OECD, Paris, France
Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2:751–760
Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WA, Seaton A, Stone V, Brown S, Macnee W, Donaldson K (2008) Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. Nat Nanotechnol 3:423–428
Porter D, Sriram K, Wolfarth M, Jefferson A, Schwegler-Berry D, Andrew ME, Castranova V (2008) A biocompatible medium for nanoparticle dispersion. Nanotoxicology 2:144–154
Schmid W (1976) The micronucleus test for cytogenetic analysis. In: Hollaender A (ed) Chemical mutagens: principles and methods for their detection, vol 4. Plenum Press, New York, pp 31–53
Szendi K, Varga C (2008) Lack of genotoxicity of carbon nanotubes in a pilot study. Anticancer Res 28:349–352
Takagi A, Hirose A, Nishimura T, Fukumori N, Ogata A, Ohashi N, Kitajima S, Kanno J (2008) Induction of mesothelioma in p53 ± mouse by intraperitoneal application of multi-wall carbon nanotube. J Toxicol Sci 33:105–116
Tran CL, Hankin SM, Ross B, Aitken RJ, Jones AD, Donaldson K, Stone V, Tantra R (2008) An outline scoping study to determine whether high aspect ratio nanoparticles (HARN) should raise the same concerns as do asbestos fibres, IOM Report on Project CB0406, Edinburgh, UK
Wirnitzer U, Herbold B, Voetz M, Ragot J (2009) Studies on the in vitro genotoxicity of baytubes®, agglomerates of engineered multi-walled carbon-nanotubes (MWCNT). Toxicol Lett 186:160–165
You CC, De M, Rotello VM (2005) Monolayer-protected nanoparticle–protein interactions. Curr Opin Chem Biol 9:639–646