Pulmonary response to surface-coated nanotitanium dioxide particles includes induction of acute phase response genes, inflammatory cascades, and changes in microRNAs: A toxicogenomic study

Environmental and Molecular Mutagenesis

Volumn 52, Issue 6, 2011, Pages 425-439

  Halappanavar, Sabina ^a   Jackson, Petra ^b,c   Williams, Andrew ^a   Jensen, Keld A ^b   Hougaard, Karin S ^b   Vogel, Ulla ^b,c,d   Yauk, Carole L ^a   Wallin, Håkan ^b,e  

^a HEALTH CANADA   (Canada)

^b NATIONAL RESEARCH CENTRE FOR THE WORKING ENVIRONMENT   (Denmark)

^c ROSKILDE UNIVERSITY   (Denmark)

^d TECHNICAL UNIVERSITY OF DENMARK   (Denmark)

^e UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

Gene expression; Inflammation; MicroRNA; Nanotitanium dioxide

Indexed keywords

ALPHA CHEMOKINE; COMPLEMENT COMPONENT C1; COMPLEMENT COMPONENT C3; MESSENGER RNA; MICRORNA; MICRORNA 135B; MICRORNA 449A; NANOPARTICLE; SERUM AMYLOID A; SERUM AMYLOID A 1; SERUM AMYLOID A 3; TITANIUM DIOXIDE; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG;

ACUTE PHASE RESPONSE; ANIMAL TISSUE; COATED PARTICLE; CONTROLLED STUDY; DNA MICROARRAY; ENVIRONMENTAL EXPOSURE; FEMALE; GENE EXPRESSION; IMMUNE RESPONSE; INHALATION; MOUSE; NONHUMAN; PHYSICAL CHEMISTRY; PNEUMONIA; POLYMERASE CHAIN REACTION; PROTEIN ANALYSIS; REAL TIME POLYMERASE CHAIN REACTION; REVIEW; TOXICOGENETICS; TRACHEOBRONCHIAL TOILET; UPREGULATION;

ANIMALS; CHEMOKINES; FEMALE; LUNG; MICE; MICRORNAS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; POLYMERASE CHAIN REACTION; SERUM AMYLOID A PROTEIN; TITANIUM; TOXICOGENETICS;

MUS;

EID: 79959904775     PISSN: 08936692     EISSN: 10982280     Source Type: Journal    
DOI: 10.1002/em.20639     Document Type: Review

References (98)

1. (IARC) IAfRoC. Feb. 2006. Titanium dioxide (IARC Group 2B). Summary of data reported.
2. Alvo M, Liu Z, Williams A, Yauk C. 2010. Testing for mean and correlation changes in microarray experiments: An application for pathway analysis. BMC Bioinformatics 11: 60.
3. Andre E, Stoeger T, Takenaka S, Bahnweg M, Ritter B, Karg E, Lentner B, Reinhard C, Schulz H, Wjst M. 2006. Inhalation of ultrafine carbon particles triggers biphasic pro-inflammatory response in the mouse lung. Eur Respir J 28: 275-285.
4. Baggs RB, Ferin J, Oberdorster G. 1997. Regression of pulmonary lesions produced by inhaled titanium dioxide in rats. Vet Pathol 34: 592-597.
5. Bermudez E, Mangum JB, Asgharian B, Wong BA, Reverdy EE, Janszen DB, Hext PM, Warheit DB, Everitt JI. 2002. Long-term pulmonary responses of three laboratory rodent species to subchronic inhalation of pigmentary titanium dioxide particles. Toxicol Sci 70: 86-97.
6. Bermudez E, Mangum JB, Wong BA, Asgharian B, Hext PM, Warheit DB, Everitt JI. 2004. Pulmonary responses of mice, rats, and hamsters to subchronic inhalation of ultrafine titanium dioxide particles. Toxicol Sci 77: 347-357.
7. Bhattacharjee A, Richards WG, Staunton J, Li C, Monti S, Vasa P, Ladd C, Beheshti J, Bueno R, Gillette M, Loda M, Weber G, Mark EJ, Lander ES, Wong W, Johnson BE, Golub TR, Sugarbaker DJ, Meyerson M. 2001. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA 98: 13790-13795.
8. Bhattacharya K, Cramer H, Albrecht C, Schins R, Rahman Q, Zimmermann U, Dopp E. 2008. Vanadium pentoxide-coated ultrafine titanium dioxide particles induce cellular damage and micronucleus formation in V79 cells. J Toxicol Environ Health A 71: 976-980.
9. Bolstad BM, Irizarry RA, Astrand M, Speed TP. 2003. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19: 185-193.
10. Borm PJ, Robbins D, Haubold S, Kuhlbusch T, Fissan H, Donaldson K, Schins R, Stone V, Kreyling W, Lademann J, Krutmann J, Warheit D, Oberdorster E. 2006. The potential risks of nanomaterials: A review carried out for ECETOC. Part Fibre Toxicol 3: 11.
11. Bueno MJ, de Castro IP, Malumbres M. 2008. Control of cell proliferation pathways by microRNAs. Cell Cycle 7: 3143-3148.
12. Carleton M, Cleary MA, Linsley PS. 2007. MicroRNAs and cell cycle regulation. Cell Cycle 6: 2127-2132.
13. Chen HW, Su SF, Chien CT, Lin WH, Yu SL, Chou CC, Chen JJ, Yang PC. 2006. Titanium dioxide nanoparticles induce emphysema-like lung injury in mice. FASEB J 20: 2393-2395.
14. Chen J, Dong X, Zhao J, Tang G. 2009. In vivo acute toxicity of titanium dioxide nanoparticles to mice after intraperitioneal injection. J Appl Toxicol 29: 330-337.
15. Croce CM. 2009. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 10: 704-714.
16. Cui X, Hwang JT, Qiu J, Blades NJ, Churchill GA. 2005. Improved statistical tests for differential gene expression by shrinking variance components estimates. Biostatistics 6: 59-75.
17. Cullen RT, Tran CL, Buchanan D, Davis JM, Searl A, Jones AD, Donaldson K. 2000. Inhalation of poorly soluble particles. I. Differences in inflammatory response and clearance during exposure. Inhal Toxicol 12: 1089-1111.
18. Dankovic D, Kuempel E, Wheeler M. 2007. An approach to risk assessment for TiO2. Inhal Toxicol 19( Suppl 1): 205-212.
19. de Haar C, Hassing I, Bol M, Bleumink R, Pieters R. 2006. Ultrafine but not fine particulate matter causes airway inflammation and allergic airway sensitization to co-administered antigen in mice. Clin Exp Allergy 36: 1469-1479.
20. Driscoll KE, Hassenbein DG, Carter J, Poynter J, Asquith TN, Grant RA, Whitten J, Purdon MP, Takigiku R. 1993. Macrophage inflammatory proteins 1 and 2: Expression by rat alveolar macrophages, fibroblasts, and epithelial cells and in rat lung after mineral dust exposure. Am J Respir Cell Mol Biol 8: 311-318.
21. Drumm K, Schindler H, Buhl R, Kustner E, Smolarski R, Kienast K. 1999. Indoor air pollutants stimulate interleukin-8-specific mRNA expression and protein secretion of alveolar macrophages. Lung 177: 9-19.
22. Farraj AK, Hazari MS, Haykal-Coates N, Lamb C, Winsett DW, Ge Y, Ledbetter AD, Carll AP, Bruno M, Ghio A, Costa DL. 2010. ST depression, arrhythmia, vagal dominance, and reduced cardiac microRNA in particulate-exposed rats. Am J Respir Cell Mol Biol (in press).
23. Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, Aderem A. 2004. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432: 917-921.
24. Ganapathi MK, May LT, Schultz D, Brabenec A, Weinstein J, Sehgal PB, Kushner I. 1988. Role of interleukin-6 in regulating synthesis of C-reactive protein and serum amyloid A in human hepatoma cell lines. Biochem Biophys Res Commun 157: 271-277.
25. Garzon R, Calin GA, Croce CM. 2009. MicroRNAs in cancer. Annu Rev Med 60: 167-179.
26. Golpon HA, Coldren CD, Zamora MR, Cosgrove GP, Moore MD, Tuder RM, Geraci MW, Voelkel NF. 2004. Emphysema lung tissue gene expression profiling. Am J Respir Cell Mol Biol 31: 595-600.
27. Granville CA, Dennis PA. 2005. An overview of lung cancer genomics and proteomics. Am J Respir Cell Mol Biol 32: 169-176.
28. Guil S, Esteller M. 2009. DNA methylomes, histone codes and miRNAs: Tying it all together. Int J Biochem Cell Biol 41: 87-95.
29. Hanahan D, Weinberg RA. 2000. The hallmarks of cancer. Cell 100: 57-70.
30. Heinrich U, Fuhst R, Rittinghausen S, Creutzenberg O, Bellmann B, Koch W, Levesen K. 1995. Chronic inhalation exposure of wistar rats and two different strains of mice to diesel engine exhaust, carbon black, and titanium dioxide. Inhal Toxicol 7: 533-556.
31. Hiratsuka S, Watanabe A, Sakurai Y, Akashi-Takamura S, Ishibashi S, Miyake K, Shibuya M, Akira S, Aburatani H, Maru Y. 2008. The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol 10: 1349-1355.
32. Benjamini Y, Hochberg Y. 1995. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J R Stat Soc Ser B Stat Methodol 57: 289-300.
33. Hougaard KS, Jackson P, Jensen KA, Sloth JJ, Loschner K, Larsen EH, Birkedal RK, Vibenholt A, Boisen AM, Wallin H, Vogel U. 2010. Effects of prenatal exposure to surface-coated nanosized titanium dioxide (UV-Titan). A study in mice. Part Fibre Toxicol 7: 16.
34. Hougaard KS, Jensen KA, Nordly P, Taxvig C, Vogel U, Saber AT, Wallin H. 2008. Effects of prenatal exposure to diesel exhaust particles on postnatal development, behavior, genotoxicity and inflammation in mice. Part Fibre Toxicol 5: 3
35. Huang da W, Sherman BT, Lempicki RA. 2009. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4: 44-57.
36. Hudder A, Novak RF. 2008. miRNAs: Effectors of environmental influences on gene expression and disease. Toxicol Sci 103: 228-240.
37. Jacobsen NR, Moller P, Jensen KA, Vogel U, Ladefoged O, Loft S, Wallin H. 2009. Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice. Part Fibre Toxicol 6: 2
38. Jardim MJ, Fry RC, Jaspers I, Dailey L, Diaz-Sanchez D. 2009. Disruption of microRNA expression in human airway cells by diesel exhaust particles is linked to tumorigenesis-associated pathways. Environ Health Perspect 117: 1745-1751.
39. Jensen LE, Whitehead AS. 1998. Regulation of serum amyloid A protein expression during the acute-phase response. Biochem J 334(Part 3): 489-503.
40. Jeyaseelan S, Manzer R, Young SK, Yamamoto M, Akira S, Mason RJ, Worthen GS. 2005. Induction of CXCL5 during inflammation in the rodent lung involves activation of alveolar epithelium. Am J Respir Cell Mol Biol 32: 531-539.
41. Jiang SL, Lozanski G, Samols D, Kushner I. 1995. Induction of human serum amyloid A in Hep 3B cells by IL-6 and IL-1 beta involves both transcriptional and post-transcriptional mechanisms. J Immunol 154: 825-831.
42. Jin P, Wang E, Ren J, Childs R, Shin JW, Khuu H, Marincola FM, Stroncek DF. 2008. Differentiation of two types of mobilized peripheral blood stem cells by microRNA and cDNA expression analysis. J Transl Med 6: 39.
43. Kerr MK. 2003. Design considerations for efficient and effective microarray studies. Biometrics 59: 822-828.
44. Kerr MK, Churchill GA. 2001. Bootstrapping cluster analysis: Assessing the reliability of conclusions from microarray experiments. Proc Natl Acad Sci USA 98: 8961-8965.
45. Kerr MK, Churchill GA. 2007. Statistical design and the analysis of gene expression microarray data. Genet Res 89: 509-514.
46. Kim VN, Han J, Siomi MC. 2009. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10: 126-139.
47. Kong W, Zhao JJ, He L, Cheng JQ. 2009. Strategies for profiling microRNA expression. J Cell Physiol 218: 22-25.
48. Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, Pfeffer S, Rice A, Kamphorst AO, Landthaler M, Lin C, Socci ND, Hermida L, Fulci V, Chiaretti S, Foa R, Schliwka J, Fuchs U, Novosel A, Muller RU, Schermer B, Bissels U, Inman J, Phan Q, Chien M, Weir DB, hoksi R, De Vita G, Frezzetti D, Trompeter HI, Hornung V, Teng G, Hartmann G, Palkovits M, Di Lauro R, Wernet P, Macino G, Rogler CE, Nagle JW, Ju J, Papavasiliou FN, Benzing T, Lichter P, Tam W, Brownstein MJ, Bosio A, Borkhardt A, Russo JJ, Sander C, Zavolan M, Tuschl T. 2007. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129: 1401-1414.
49. Lee KP, Trochimowicz HJ, Reinhardt CF. 1985. Pulmonary response of rats exposed to titanium dioxide (TiO2) by inhalation for two years. Toxicol Appl Pharmacol 79: 179-192.
50. Lema C, Cunningham MJ. 2010. MicroRNAs and their implications in toxicological research. Toxicol Lett 198: 100-105.
51. Lowell CA, Stearman RS, Morrow JF. 1986. Transcriptional regulation of serum amyloid A gene expression. J Biol Chem 261: 8453-8461.
52. Lu TX, Munitz A, Rothenberg ME. 2009. MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression. J Immunol 182: 4994-5002.
53. Lynam-Lennon N, Maher SG, Reynolds JV. 2009. The roles of microRNA in cancer and apoptosis. Biol Rev Camb Philos Soc 84: 55-71.
54. Ma-Hock L, Burkhardt S, Strauss V, Gamer AO, Wiench K, van Ravenzwaay B, Landsiedel R. 2009. Development of a short-term inhalation test in the rat using nano-titanium dioxide as a model substance. Inhal Toxicol 21: 102-118.
55. Meek RL, Benditt EP. 1986. Amyloid A gene family expression in different mouse tissues. J Exp Med 164: 2006-2017.
56. Mei N, Fuscoe JC, Lobenhofer EK, Guo L. 2010. Application of microarray-based analysis of gene expression in the field of toxicogenomics. Methods Mol Biol 597: 227-241.
57. Morrow JF, Stearman RS, Peltzman CG, Potter DA. 1981. Induction of hepatic synthesis of serum amyloid A protein and actin. Proc Natl Acad Sci USA 78: 4718-4722.
58. Nakao I, Kanaji S, Ohta S, Matsushita H, Arima K, Yuyama N, Yamaya M, Nakayama K, Kubo H, Watanabe M, Sagara H, Sugiyama K, Tanaka H, Toda S, Hayashi H, Inoue H, Hoshino T, Shiraki A, Inoue M, Suzuki K, Aizawa H, Okinami S, Nagai H, Hasegawa M, Fukuda T, Green ED, Izuhara K. 2008. Identification of pendrin as a common mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease. J Immunol 180: 6262-6269.
59. Ning W, Li CJ, Kaminski N, Feghali-Bostwick CA, Alber SM, Di YP, Otterbein SL, Song R, Hayashi S, Zhou Z, Pinsky DJ, Watkins SC, Pilewski JM, Sciurba FC, Peters DG, Hogg JC, Choi AM. 2004. Comprehensive gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease. Proc Natl Acad Sci USA 101: 14895-14900.
60. Nitto T, Inoue T, Node K. 2008. Alternative spliced variants in the pantetheinase family of genes expressed in human neutrophils. Gene 426: 57-64.
61. Noonan EJ, Place RF, Pookot D, Basak S, Whitson JM, Hirata H, Giardina C, Dahiya R. 2009. miR-449a targets HDAC-1 and induces growth arrest in prostate cancer. Oncogene 28: 1714-1724.
62. Oberdorster G. 1995. Lung particle overload: Implications for occupational exposures to particles. Regul Toxicol Pharmacol 21: 123-135.
63. Oberdorster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W, Lai D, Olin S, Monteiro-Riviere N, Warheit D, Yang H. 2005a. Principles for characterizing the potential human health effects from exposure to nanomaterials: Elements of a screening strategy. Part Fibre Toxicol 2: 8.
64. Oberdorster G, Oberdorster E, Oberdorster J. 2005b. Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113: 823-839.
65. Oberdorster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W, Cox C. 2004. Translocation of inhaled ultrafine particles to the brain. Inhal Toxicol 16: 437-445.
66. Oberdorster G, Sharp Z, Atudorei V, Elder A, Gelein R, Lunts A, Kreyling W, Cox C. 2002. Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J Toxicol Environ Health A 65: 1531-1543.
67. Park EJ, Kim H, Kim Y, Yi J, Choi K, Park K. 2010. Inflammatory responses may be induced by a single intratracheal instillation of iron nanoparticles in mice. Toxicology 275: 65-71.
68. Park EJ, Yoon J, Choi K, Yi J, Park K. 2009. Induction of chronic inflammation in mice treated with titanium dioxide nanoparticles by intratracheal instillation. Toxicology 260: 37-46.
69. Pfaffl MW, Horgan GW, Dempfle L. 2002. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 30: e36.
70. Ploner A. 2008. Heatplus: A heat map displaying covariates and coloring clusters. R package Version 1.14.0.
71. Pope CAIII, Hansen ML, Long RW, Nielsen KR, Eatough NL, Wilson WE, Eatough DJ. 2004. Ambient particulate air pollution, heart rate variability, and blood markers of inflammation in a panel of elderly subjects. Environ Health Perspect 112: 339-345.
72. Pott F, Althoff G-H, Roller M, Hohr D, Friemann J. 1998. High acute toxicity of hydrophobic ultrafine titanium dioxide in an intratracheal study with several dusts in rats. In: Mohr U, Dungworth DL, editors. ILSI Monographs Relationship Between Respiratory Disease and Exposure to Air Pollution. Washington, DC: ILSI Press. pp 270-277.
73. R-Development-Core-Team. 2004. R: A Language and Environment for Statistical Computing. TRDC.
74. R-Development-Core-Team. 2009. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing.
75. Rahman Q, Lohani M, Dopp E, Pemsel H, Jonas L, Weiss DG, Schiffmann D. 2002. Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts. Environ Health Perspect 110: 797-800.
76. Rehn B, Seiler F, Rehn S, Bruch J, Maier M. 2003. Investigations on the inflammatory and genotoxic lung effects of two types of titanium dioxide: Untreated and surface treated. Toxicol Appl Pharmacol 189: 84-95.
77. Renwick LC, Brown D, Clouter A, Donaldson K. 2004. Increased inflammation and altered macrophage chemotactic responses caused by two ultrafine particle types. Occup Environ Med 61: 442-447.
78. Rossi EM, Pylkkanen L, Koivisto AJ, Vippola M, Jensen KA, Miettinen M, Sirola K, Nykasenoja H, Karisola P, Stjernvall T, Vanhala E, Kiilunen M, Pasanen P, Makinen M, Hameri K, Joutsensaari J, Tuomi T, Jokiniemi J, Wolff H, Savolainen K, Matikainen S, Alenius H. 2010. Airway exposure to silica-coated TiO2 nanoparticles induces pulmonary neutrophilia in mice. Toxicol Sci 113: 422-433.
79. Ruckerl R, Ibald-Mulli A, Koenig W, Schneider A, Woelke G, Cyrys J, Heinrich J, Marder V, Frampton M, Wichmann HE, Peters A. 2006. Air pollution and markers of inflammation and coagulation in patients with coronary heart disease. Am J Respir Crit Care Med 173: 432-441.
80. Saber AT, Halappanavar S, Folkmann JK, Bornholdt J, Boisen AM, Moller P, Williams A, Yauk C, Vogel U, Loft S, Wallin H. 2009. Lack of acute phase response in the livers of mice exposed to diesel exhaust particles or carbon black by inhalation. Part Fibre Toxicol 6: 12.
81. Sarver AL, French AJ, Borralho PM, Thayanithy V, Oberg AL, Silverstein KA, Morlan BW, Riska SM, Boardman LA, Cunningham JM, Subramanian S, Wang L, Smyrk TC, Rodrigues CM, Thibodeau SN, Steer CJ. 2009. Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states. BMC Cancer 9: 401.
82. Sayes CM, Wahi R, Kurian PA, Liu Y, West JL, Ausman KD, Warheit DB, Colvin VL. 2006. Correlating nanoscale titania structure with toxicity: A cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. Toxicol Sci 92: 174-185.
83. Schneeman TA, Bruno ME, Schjerven H, Johansen FE, Chady L, Kaetzel CS. 2005. Regulation of the polymeric Ig receptor by signaling through TLRs 3 and 4: Linking innate and adaptive immune responses. J Immunol 175: 376-384.
84. Spira A, Beane J, Pinto-Plata V, Kadar A, Liu G, Shah V, Celli B, Brody JS. 2004. Gene expression profiling of human lung tissue from smokers with severe emphysema. Am J Respir Cell Mol Biol 31: 601-610.
85. Sun BK, Tsao H. 2008. Small RNAs in development and disease. J Am Acad Dermatol 59: 725-737; quiz 738-740.
86. Takaya T, Ono K, Kawamura T, Takanabe R, Kaichi S, Morimoto T, Wada H, Kita T, Shimatsu A, Hasegawa K. 2009. MicroRNA-1 and microRNA-133 in spontaneous myocardial differentiation of mouse embryonic stem cells. Circ J 73: 1492-1497.
87. Taylor EL, Gant TW. 2008. Emerging fundamental roles for non-coding RNA species in toxicology. Toxicology 246: 34-39.
88. Tran CL, Buchanan D, Cullen RT, Searl A, Jones AD, Donaldson K. 2000. Inhalation of poorly soluble particles. II. Influence of particle surface area on inflammation and clearance. Inhal Toxicol 12: 1113-1126.
89. Tsitsiou E, Lindsay MA. 2009. microRNAs and the immune response. Curr Opin Pharmacol 9: 514-520.
90. van Ravenzwaay B, Landsiedel R, Fabian E, Burkhardt S, Strauss V, Ma-Hock L. 2009. Comparing fate and effects of three particles of different surface properties: Nano-TiO(2), pigmentary TiO(2) and quartz. Toxicol Lett 186: 152-159.
91. Wang JJ, Sanderson BJ, Wang H. 2007. Cyto- and genotoxicity of ultrafine TiO2 particles in cultured human lymphoblastoid cells. Mutat Res 628: 99-106.
92. Wang Y, Liang Y, Lu Q. 2008. MicroRNA epigenetic alterations: Predicting biomarkers and therapeutic targets in human diseases. Clin Genet 74: 307-315.
93. Warheit DB, Brock WJ, Lee KP, Webb TR, Reed KL. 2005. Comparative pulmonary toxicity inhalation and instillation studies with different TiO2 particle formulations: Impact of surface treatments on particle toxicity. Toxicol Sci 88: 514-524.
94. Warheit DB, Frame SR. 2006. Characterization and reclassification of titanium dioxide-related pulmonary lesions. J Occup Environ Med 48: 1308-1313.
95. Warheit DB, Hansen JF, Yuen IS, Kelly DP, Snajdr SI, Hartsky MA. 1997. Inhalation of high concentrations of low toxicity dusts in rats results in impaired pulmonary clearance mechanisms and persistent inflammation. Toxicol Appl Pharmacol 145: 10-22.
96. Warheit DB, Webb TR, Sayes CM, Colvin VL, Reed KL. 2006. Pulmonary instillation studies with nanoscale TiO2 rods and dots in rats: Toxicity is not dependent upon particle size and surface area. Toxicol Sci 91: 227-236.
97. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. 2009. Many roads to maturity: MicroRNA biogenesis pathways and their regulation. Nat Cell Biol 11: 228-234.
98. Wu H, Kerr M, Cui X, Churchill G. 2003. Maanova: A Software Package for the Analysis of Spotted cDNA Microarray Experiments. New York: Springer. pp 313-341.