Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling in Rat Lung, Blood, and Serum for Assessment of Laser Printer-Emitted Nanoparticle Inhalation Exposure-Induced Disease Risks
by
Nancy Lan Guo 1,*
, Tuang Yeow Poh 2, Sandra Pirela 3, Mariana T. Farcas 4, Sanjay H. Chotirmall 2, Wai Kin Tham 5, Sunil S. Adav 5, Qing Ye 1, Yongyue Wei 6, Sipeng Shen 2, David C. Christiani 2, Kee Woei Ng 3,7,8, Treye Thomas 9, Yong Qian 4 and Philip Demokritou 3
Nancy Lan Guo 1,*, Tuang Yeow Poh 2, Sandra Pirela 3, Mariana T. Farcas 4, Sanjay H. Chotirmall 2, Wai Kin Tham 5, Sunil S. Adav 5, Qing Ye 1, Yongyue Wei 6, Sipeng Shen 2, David C. Christiani 2, Kee Woei Ng 3,7,8, Treye Thomas 9, Yong Qian 4 and Philip Demokritou 3
1
West Virginia University Cancer Institute/School of Public Health, West Virginia University, Morgantown, WV 26506, USA
2
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
3
Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA
4
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA
5
Singapore Phenome Centre, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore
6
Key Lab for Modern Toxicology, Department of Epidemiology and Biostatistics and Ministry of Education (MOE), School of Public Health, Nanjing Medical University, Nanjing 210029, China
7
School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore
8
Environmental Chemistry and Materials Centre, Nanyang Environment & Water Research Institute, Singapore 637141, Singapore
9
Office of Hazard Identification and Reduction, U.S. Consumer Product Safety Commission, Rockville, MD 20814, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(24), 6348; https://doi.org/10.3390/ijms20246348
Received: 2 December 2019 / Revised: 12 December 2019 / Accepted: 13 December 2019 / Published: 16 December 2019
(This article belongs to the Special Issue Advances in Nanostructured Materials between Pharmaceutics and Biomedicine)
Laser printer-emitted nanoparticles (PEPs) generated from toners during printing represent one of the most common types of life cycle released particulate matter from nano-enabled products. Toxicological assessment of PEPs is therefore important for occupational and consumer health protection. Our group recently reported exposure to PEPs induces adverse cardiovascular responses including hypertension and arrythmia via monitoring left ventricular pressure and electrocardiogram in rats. This study employed genome-wide mRNA and miRNA profiling in rat lung and blood integrated with metabolomics and lipidomics profiling in rat serum to identify biomarkers for assessing PEPs-induced disease risks. Whole-body inhalation of PEPs perturbed transcriptional activities associated with cardiovascular dysfunction, metabolic syndrome, and neural disorders at every observed time point in both rat lung and blood during the 21 days of exposure. Furthermore, the systematic analysis revealed PEPs-induced transcriptomic changes linking to other disease risks in rats, including diabetes, congenital defects, auto-recessive disorders, physical deformation, and carcinogenesis. The results were also confirmed with global metabolomics profiling in rat serum. Among the validated metabolites and lipids, linoleic acid, arachidonic acid, docosahexanoic acid, and histidine showed significant variation in PEPs-exposed rat serum. Overall, the identified PEPs-induced dysregulated genes, molecular pathways and functions, and miRNA-mediated transcriptional activities provide important insights into the disease mechanisms. The discovered important mRNAs, miRNAs, lipids and metabolites may serve as candidate biomarkers for future occupational and medical surveillance studies. To the best of our knowledge, this is the first study systematically integrating in vivo, transcriptomics, metabolomics, and lipidomics to assess PEPs inhalation exposure-induced disease risks using a rat model.
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Keywords:
printer emitted nanoparticles; inhalation; transcriptomics; metabolomics; lipidomics; biomarkers; nanotoxicity
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MDPI and ACS Style
Guo, N.L.; Poh, T.Y.; Pirela, S.; Farcas, M.T.; Chotirmall, S.H.; Tham, W.K.; Adav, S.S.; Ye, Q.; Wei, Y.; Shen, S.; Christiani, D.C.; Ng, K.W.; Thomas, T.; Qian, Y.; Demokritou, P. Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling in Rat Lung, Blood, and Serum for Assessment of Laser Printer-Emitted Nanoparticle Inhalation Exposure-Induced Disease Risks. Int. J. Mol. Sci. 2019, 20, 6348.
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