title: Exploring the potential role of tungsten carbide cobalt (WC-Co) nanoparticle internalization in observed toxicity toward lung epithelial cells in vitro.
abstract: Tungsten carbide cobalt (WC-Co) has been recognized as a workplace inhalation hazard in the manufacturing, mining and drilling industries by the National Institute of Occupational Safety and Health. Exposure to WC-Co is known to cause "hard metal lung disease" but the relationship between exposure, toxicity and development of disease remain poorly understood. To better understand this relationship, the present study examined the role of WC-Co particle size and internalization on toxicity using lung epithelial cells. We demonstrated that nano- and micro-WC-Co particles exerted toxicity in a dose- and time-dependent manner and that nano-WC-Co particles caused significantly greater toxicity at lower concentrations and shorter exposure times compared to micro-WC-Co particles. WC-Co particles in the nano-size range (not micron-sized) were internalized by lung epithelial cells, which suggested that internalization may play a key role in the enhanced toxicity of nano-WC-Co particles over micro-WC-Co particles. Further exploration of the internalization process indicated that there may be multiple mechanisms involved in WC-Co internalization such as actin and microtubule based cytoskeletal rearrangements. These findings support our hypothesis that WC-Co particle internalization contributes to cellular toxicity and suggest that therapeutic treatments inhibiting particle internalization may serve as prophylactic approaches for those at risk of WC-Co particle exposure.
authors.affiliation: Biomaterials, Bioengineering & Nanotechnology Laboratory, Department of Orthopaedics, School of Medicine, West Virginia University, Morgantown, WV 26506, USA; Pharmaceutical and Pharmacological Sciences Graduate Program, School of Pharmacy, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Armstead
authors.affiliation: Biomaterials, Bioengineering & Nanotechnology Laboratory, Department of Orthopaedics, School of Medicine, West Virginia University, Morgantown, WV 26506, USA; E.J. Van Liere Research Program, School of Medicine, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Arena
authors.affiliation: Biomaterials, Bioengineering & Nanotechnology Laboratory, Department of Orthopaedics, School of Medicine, West Virginia University, Morgantown, WV 26506, USA; Pharmaceutical and Pharmacological Sciences Graduate Program, School of Pharmacy, West Virginia University, Morgantown, WV 26506, USA; E.J. Van Liere Research Program, School of Medicine, West Virginia University, Morgantown, WV 26506, USA; Mary Babb Randolph Cancer Center, Morgantown, WV 26506, USA. Electronic address: bili@hsc.wvu.edu.
authors.forename: Bingyun
authors.initials: B
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003035:Cobalt / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053768:Metal Nanoparticles / Q000633:toxicity*; D016273:Occupational Exposure; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D013997:Time Factors; D017973:Tungsten Compounds / Q000378:metabolism / Q000633:toxicity*
chemical_list: D017973:Tungsten Compounds; C002802:tungsten carbide; D003035:Cobalt
keywords: Hard metal; Internalization; Lung disease; Nanoparticle; Nanotoxicity; Pulmonary exposure
references.citation: Am J Respir Crit Care Med. 2007 Jul 1;176(1):70-7
references.pmid: 17363774
references.citation: J Cell Biochem. 2003 Apr 1;88(5):885-98
references.pmid: 12616528
references.citation: Am J Epidemiol. 1998 Aug 1;148(3):241-8
references.pmid: 9690360
references.citation: J Expo Sci Environ Epidemiol. 2009 Jul;19(5):475-91
references.pmid: 18628793
references.citation: Acc Chem Res. 2013 Mar 19;46(3):782-91
references.pmid: 23194178
references.citation: Wien Med Wochenschr. 1985 Nov 15;135(21):523-5
references.pmid: 4082603
references.citation: Toxicol In Vitro. 2011 Dec;25(8):1619-29
references.pmid: 21723938
references.citation: Clin Chest Med. 1992 Jun;13(2):269-79
references.pmid: 1511554
references.citation: Toxicol Sci. 2009 Jul;110(1):138-55
references.pmid: 19414515
references.citation: J Toxicol Environ Health B Crit Rev. 2011;14(8):593-632
references.pmid: 22008094
references.citation: Ind Health. 2007 Dec;45(6):793-803
references.pmid: 18212475
references.citation: Toxicol Lett. 1992 Apr;60(2):203-10
references.pmid: 1570634
references.citation: Chem Res Toxicol. 1995 Jun;8(4):600-6
references.pmid: 7548741
references.citation: Sci Total Environ. 1994 Jun 30;150(1-3):187-96
references.pmid: 7939595
references.citation: Carcinogenesis. 2003 Nov;24(11):1793-800
references.pmid: 12949052
references.citation: Occup Environ Med. 2001 Oct;58(10):631-4
references.pmid: 11555683
references.citation: Chem Res Toxicol. 2012 Sep 17;25(9):1885-92
references.pmid: 22799765
references.citation: Carcinogenesis. 1997 Jan;18(1):177-84
references.pmid: 9054604
references.citation: J Thorac Imaging. 2005 Nov;20(4):301-4
references.pmid: 16282911
references.citation: Cancer Biomark. 2010;6(3-4):221-4
references.pmid: 20660967
references.citation: Mater Today (Kidlington). 2013 Jun 1;16(6):229-241
references.pmid: 25125992
references.citation: Scand J Work Environ Health. 1996 Feb;22(1):62-5
references.pmid: 8685677
references.citation: Exp Biol Med (Maywood). 2010 Sep;235(9):1025-33
references.pmid: 20719818
references.citation: Toxicol Appl Pharmacol. 1992 Jan;112(1):41-50
references.pmid: 1733047
references.citation: Int J Nanomedicine. 2012;7:3951-9
references.pmid: 22866004
references.citation: Arch Environ Occup Health. 2008 Summer;63(2):51-70
references.pmid: 18628077
references.citation: Sci Total Environ. 1994 Jun 30;150(1-3):219-21
references.pmid: 7939600
references.citation: Am J Respir Cell Mol Biol. 2001 Feb;24(2):108-15
references.pmid: 11159043
references.citation: Inhal Toxicol. 2009 Jul;21 Suppl 1:115-22
references.pmid: 19558243
references.citation: PLoS One. 2011;6(9):e24438
references.pmid: 21949717
references.citation: Arch Toxicol. 2012 Jul;86(7):1123-36
references.pmid: 22407301
references.citation: Sci Total Environ. 1990 Jun;95:107-17
references.pmid: 2205918
references.citation: J Hazard Mater. 2012 Aug 15;227-228:418-26
references.pmid: 22698683
references.citation: Br J Ind Med. 1962 Oct;19:239-52
references.pmid: 13970036
references.citation: Environ Res. 1995 May;69(2):108-21
references.pmid: 8608770
references.citation: Toxicol Lett. 2004 Dec 1;154(1-2):23-34
references.pmid: 15475175
references.citation: Am J Respir Crit Care Med. 2007 Jul 1;176(1):2-3
references.pmid: 17586761
references.citation: Semin Respir Crit Care Med. 2001 Aug;22(4):435-48
references.pmid: 16088691
references.citation: Environ Health Perspect. 2009 Apr;117(4):530-6
references.pmid: 19440490
references.citation: Acta Pathol Jpn. 1980 Mar;30(2):241-53
references.pmid: 7386201
references.citation: Int Arch Gewerbepathol Gewerbehyg. 1962 Nov 28;19:613-32
references.pmid: 13954264
references.citation: Environ Res. 1990 Aug;52(2):187-98
references.pmid: 2168316
references.citation: Toxicol Appl Pharmacol. 2008 Mar 1;227(2):299-312
references.pmid: 18078969
references.citation: Toxicol Lett. 2008 Aug 28;180(3):222-9
references.pmid: 18662754
references.citation: Toxicol Appl Pharmacol. 2009 Dec 15;241(3):260-8
references.pmid: 19747498
references.citation: Arch Toxicol. 2013 Feb;87(2):259-68
references.pmid: 23052192
references.citation: Hefte Unfallheilkd. 1958;56:99-103
references.pmid: 13548752
references.citation: BMC Genomics. 2010 Jan 27;11:65
references.pmid: 20105288
references.citation: Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):4930-4
references.pmid: 16549762
references.citation: Toxicol Appl Pharmacol. 2000 Jan 1;162(1):2-9
references.pmid: 10631122
references.citation: Ann Occup Hyg. 1997 Oct;41(5):515-26
references.pmid: 9332157
references.citation: J Cell Biol. 1987 Oct;105(4):1473-8
references.pmid: 3312229
references.citation: J Biol Chem. 1986 Dec 5;261(34):15974-80
references.pmid: 3023337
references.citation: In Vitr Mol Toxicol. 2000 Spring;13(1):5-16
references.pmid: 10900403
references.citation: Chem Soc Rev. 2012 Apr 7;41(7):2718-39
references.pmid: 22389111
references.citation: Arh Hig Rada Toksikol. 1963;14:261-8
references.pmid: 14191113
references.citation: J Expo Sci Environ Epidemiol. 2009 May;19(4):423-34
references.pmid: 18523457
references.citation: Arch Toxicol. 1993;67(5):347-51
references.pmid: 8396391
references.citation: J Environ Pathol Toxicol Oncol. 2010;29(1):31-40
references.pmid: 20528745
references.citation: Inhal Toxicol. 2009 Jul;21 Suppl 1:68-73
references.pmid: 19558236
references.citation: Nanotoxicology. 2015 May;9 Suppl 1:13-24
references.pmid: 23889211
references.citation: Sci Total Environ. 1994 Jun 30;150(1-3):161-5
references.pmid: 7939591
references.citation: Toxicol Appl Pharmacol. 2001 Aug 1;174(3):199-206
references.pmid: 11485380
references.citation: Nihon Kyobu Shikkan Gakkai Zasshi. 1984 Sep;22(9):804-8
references.pmid: 6521094
references.citation: Occup Med. 1987 Apr-Jun;2(2):327-44
references.pmid: 3303384
references.citation: Toxicol Appl Pharmacol. 1995 May;132(1):53-62
references.pmid: 7747285
references.citation: Australas Radiol. 1968 May;12(2):92-5
references.pmid: 5662539
references.citation: J Biol Chem. 1999 Apr 9;274(15):10203-12
references.pmid: 10187805
references.citation: Am Ind Hyg Assoc J. 1975 Jan;36(1):17-25
references.pmid: 1111264
references.citation: Sarcoidosis. 1992 Sep;9(2):104-17
references.pmid: 1344051
references.citation: Toxicol Appl Pharmacol. 1999 Jun 15;157(3):178-91
references.pmid: 10373402
references.citation: Eur J Cell Biol. 1995 May;67(1):57-72
references.pmid: 7543847
references.citation: Int J Nanomedicine. 2011;6:3281-93
references.pmid: 22228996
references.citation: Res Rep Health Eff Inst. 2011 Dec;(164):3-48
references.pmid: 22329339
references.citation: Aquat Toxicol. 2009 Jun 28;93(2-3):91-9
references.pmid: 19439373
references.citation: Mutagenesis. 2003 Mar;18(2):177-86
references.pmid: 12621074
references.citation: Am J Ind Med. 1994 Nov;26(5):585-95
references.pmid: 7832207
references.citation: Toxicol In Vitro. 2012 Mar;26(2):323-34
references.pmid: 22198050
references.citation: J Thorac Imaging. 2002 Oct;17(4):314-8
references.pmid: 12362071
references.citation: Proc Natl Acad Sci U S A. 1979 Jan;76(1):86-90
references.pmid: 284377
references.citation: Sci Total Environ. 1994 Jun 30;150(1-3):65-8
references.pmid: 7939610
references.citation: Cancer Biomark. 2010;6(3-4):197-210
references.pmid: 20660965
references.citation: Eur Respir J. 2009 Sep;34(3):559-67
references.pmid: 19696157