奈米金屬微粒引發健康危害之動物實驗評估

Health Hazards Evaluation for Workers Exposed to Metal Nanoparticles by Animal Study

潘致弘(Chih-Hong Pan)；洪琨景(Kun-Jing Hong)；莊凱任(Kai-Jen Chuang)；莊校奇(Hsiao-Chi Chuang)

奈米金屬微粒 ； 發炎反應 ； 氧化壓力 ； 動物實驗 ； Metal Nanoparticles ； Inflammation ； Oxidative Stress ； Animal Study

勞動及職業安全衛生研究季刊

25卷1期（2017 / 03 / 15）

47 - 59

繁體中文

本研究以呼吸道暴露模式探討奈米氧化鋅與奈米鎳微粒對肺部呼吸道發炎反應、氧化壓力、蛋白質表現、病理變化與可能肺部腫瘤的風險，進而探討奈米金屬微粒導致呼吸道健康效應之劑量效應與致病機轉。由急性（24小時）效應呼吸毒理實驗發現奈米氧化鋅與奈米鎳暴露會引發小鼠之乳酸脫氫酵素、總蛋白質、凋亡蛋白酶-3、8-氫氧-2-去氧鳥糞核糖核苷與肺鱗狀細胞癌指標p63的濃度顯著升高。將小鼠暴露於20 μg ZnONP20的肺部取出後，將其總蛋白質萃取分析肺部各蛋白質的表現情形，研究發現共有281個蛋白質表現有意義，其中有117個蛋白質的表現增加與164個蛋白質表現下降。而將小鼠暴露於20 μg NiNP20的肺部取出後，將其總蛋白質萃取分析肺部各蛋白質的表現情形，研究發現共有212個蛋白質表現有意義，其中有108個蛋白質的表現增加與104個蛋白質表現下降。因此建議奈米氧化鋅與奈米鎳暴露的事業單位加強通風改善，並以教育訓練勞工佩戴呼吸防護具，及定期維護更換呼吸防護具，嚴格要求作業勞工佩戴呼吸防護具。

This study attempted to investigate the inflammation, oxidative stress, protein expression, pathology variation and pulmonary tumor risk after the exposure of BALB/c mice to zinc oxide nanoparticles (ZnONPs) and nickel nanoparticles (NiNPs) via intratracheal instillation. We observed that lactate dehydrogenase, total protein, caspase-3, 8-hydroxy-2'-deoxyguanosine and p63 were associated with 24-hour exposure to ZnONPs and NiNPs. All the downregulated and upregulated proteins among the 281 proteins and 212 proteins in the 24-hour of ZnONPs and NiNPs exposure were analyzed to evaluate their implications for biological processes and molecular functions. There were 117 proteins upregulation and 164 proteins downregulation after 24-hour of ZnONPs exposure. Furthermore, there were 108 proteins upregulation and 104 proteins downregulation after 24-hour of NiNPs exposure. According to our findings, we suggest employers to reinforce ventilation in the workplace for reducing ZnONPs and NiNPs esxposure. We also suggest that employers must educate employees to use respiratory protector properly and provide respiratory protector for employees to use.

1. Akhtar, MJ,Ahamed, M,Kumar, S,Khan, MM,Ahmad, J,Alrokayan, SA(2012).Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen specie.International Journal of Nanomedicine,7,845-57.
2. Beckett, WS,Chalupa, DF,Pauly-Brown, A,Speers, DM,Stewart, JC,Frampton, MW(2005).Comparing inhaled ultrafine versus fine zinc oxide particles in healthy adults: a human inhalation study.American Journal of Respiratory and Critical Care Medicine,171,1129-35.
3. Chuang, HC,Hsueh, TW,Chang, CC,Hwang, JS,Chuang, KJ,Yan, YH(2013).Nickelregulated heart rate variability: the roles of oxidative stress and inflammation.Toxicology and applied pharmacology,266,298-306.
4. El Safty, A,El Mahgoub, K,Helal, S,Maksoud, NA(2008).Zinc Toxicity among Galvanization Workers in the Iron and Steel Industry.Annals of the New York Academy of Sciences,1140,256-62.
5. Fabrega, J,Luoma, SN,Tyler, CR,Galloway, TS,Lead, JR(2011).Silver nanoparticles: Behaviour and effects in the aquatic environment.Environment International,37,517-31.
6. Fine, JM,Gordon, T,Chen, LC,Kinney, P,Falcone, G,Beckett, WS(1997).Metal fume fever: Characterization of clinical and plasma IL-6 responses in controlled human exposures to zinc oxide fume at and below the threshold limit value.Journal of Occupational and Environmental Medicine,39,722-26.
7. Glat, M,Skaat, H,Menkes-Caspi, N,Margel, S,Stern, EA(2013).Age-dependent effects of microglial inhibition in vivo on Alzheimer's disease neuropathology using bioactiveconjugated iron oxide nanoparticles.Journal of nanobiotechnology,11,32.
8. Gordon, T,Fine, JM(1993).Metal fume fever.Occupational Medicine,8,504-17.
9. Ho, M,Wu, KY,Chein, HM,Chen, LC,Cheng, TJ(2011).Pulmonary toxicity of inhaled nanoscale and fine zinc oxide particles: mass and surface area as an exposure metric.Inhalation Toxicology,23,947-56.
10. Huang da, W,Sherman, BT,Lempicki, RA(2009).Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.Nature protocols,4,44-57.
11. Juang, YM,Lai, BH,Chien, HJ,Ho, M,Cheng, TJ,Lai, CC(2014).Changes in protein expression in rat bronchoalveolar lavage fluid after exposure to zinc oxide nanoparticles: an iTRAQ proteomic approach.Rapid communications in mass spectrometry,28,974-80.
12. Kim, YS,Kim, JS,Cho, HS,Rha, DS,Kim, JM,Park, JD(2008).Twenty-eight-day oral toxicity, genotoxicity, and gender-related tissue distribution of silver nanoparticles in Sprague-Dawley rats.Inhalation Toxicology,20,575-83.
13. Kumar, A,Najafzadeh, M,Jacob, BK,Dhawan, A,Anderson, D(2015).Zinc oxide nanoparticles affect the expression of p53, Ras p21 and JNKs: an ex vivo/in vitro exposure study in respiratory disease patients.Mutagenesis,30,237-45.
14. Kuschner, WG,D'Alessandro, A,Wong, H,Blanc, PD(1997).Early pulmonary cytokine responses to zinc oxide fume inhalation.Environmental Research,75,7-11.
15. Latvala, S,Hedberg, J,Di Bucchianico, S,Möller, L,Odnevall Wallinder, I,Elihn, K(2016).Nickel release, ROS generation and toxicity of Ni and NiO micro- and nanoparticles.Plos One,11,eo159684.
16. Liao, HY,Chung, YT,Lai, CH,Wang, SL,Chiang, HC,Li, LA(2013).Six-month followup study of health markers of nanomaterials among workers handling engineered nanomaterials.Nanotoxicology,Dec 3
17. Magaye, RR,Yue, X,Zou, B,Shi, H,Yu, H,Liu, K(2014).Acute toxicity of nickel nanoparticles in rats after intravenous injection.International Journal of Nanomedicine,9,1393-1402.
18. Maynard, A,Kuempel, E(2005).Airborne Nanostructured Particles and Occupational Health.Journal of Nanoparticle Research,7,587-614.
19. Merchant, J,Webby, R(2001).Metal fume fever: a case report and literature review.Emergency Medicine,13,373-75.
20. Oberdorster, G(2001).Pulmonary effects of inhaled ultrafine particles.International archives of occupational and environmental health,74,1-8.
21. Oberdorster, G,Ferin, J,Lehnert, BE(1994).Correlation between particle size, in vivo particle persistence, and lung injury.Environmental Health Perspectives,102(Suppl 5),173-79.
22. Oberdörster, G,Oberdörster, E,Oberdörster, J.(2005).Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles.Environmental Health Perspectives,113,823-39.
23. Oberdorster, G,Sharp, Z,Atudorei, V,Elder, A,Gelein, R,Kreyling, W(2004).Translocation of inhaled ultrafine particles to the brain.Inhalation Toxicology,16,437-45.
24. Oberdorster, G,Sharp, Z,Atudorei, V,Elder, A,Gelein, R,Lunts, A(2002).Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats.Journal of Toxicology and Environmental of Health. Part A.,65,1531-43.
25. Sager, TM,Kommineni, C,Castranova, V.(2008).Pulmonary response to intratracheal instillation of ultrafine versus fine titanium dioxide: role of particle surface area.Particle and Fibre Toxicology,5,17.
26. Seaton, A,MacNee, W,Donaldson, K,Godden, D(1995).Particulate air pollution and acute health effects.Lancet,345,176-78.
27. Sun, J,Wang, S,Zhao, D,Hun, FH,Weng, L,Liu, H(2011).Cytotoxicity, permeability, and inflammation of metal oxide nanoparticles in human cardiac microvascular endothelial cells: cytotoxicity, permeability, and inflammation of metal oxide nanoparticles.Cell Biology and Toxicology,27,333-42.
28. Trouiller, B,Reliene, R,Westbrook, A,Solaimani, P,Schiestl, RH(2009).Titanium Dioxide Nanoparticles Induce DNA Damage and Genetic Instability In vivo in Mice.Cancer Research,69,8784-89.