Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling in Rat Lung, Blood, and Serum for Assessment of Laser Printer-Emitted Nanoparticle Inhalation Exposure-Induced Disease Risks

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 g...

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Published inInternational Journal of Molecular Sciences Vol. 20; no. 24; p. 6348
Main Authors Guo, Nancy Lan, Poh, Tuang Yeow, Pirela, Sandra, Farcas, Mariana T., Chotirmall, Sanjay H., Tham, Wai Kin, Adav, Sunil S., Ye, Qing, Wei, Yongyue, Shen, Sipeng, Christiani, David C., Ng, Kee Woei, Thomas, Treye, Qian, Yong, Demokritou, Philip
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 16.12.2019
MDPI
Subjects
Air Pollutants
Air Pollutants - analysis
Animals
Biomarkers
Cardiovascular disease
Cell division
Diabetes
Disease
Disease - genetics
Gene expression
inhalation
Inhalation Exposure
Inhalation Exposure - adverse effects
Integrated approach
Laser printers
Lipidomics
Lung
Lung - metabolism
Male
Medicine [Science]
Metabolism
metabolomics
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
Nanoparticles
Nanoparticles - adverse effects
Nanotechnology
nanotoxicity
Printer Emitted Nanoparticles
Printing
Rats, Sprague-Dawley
Risk Factors
RNA, Messenger
RNA, Messenger - genetics
RNA, Messenger - metabolism
Rodents
Science::Medicine
Serum
Serum - metabolism
Surveillance
Toxicology
Transcriptome
Transcriptome - genetics
transcriptomics
inhalation
nanotoxicity
metabolomics
biomarkers
printer emitted nanoparticles
transcriptomics
lipidomics
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Abstract 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.
AbstractList 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.
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.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.
Author Yongyue Wei
Mariana T. Farcas
Nancy Lan Guo
Sandra V. Pirela
Wai Kin Tham
Philip Demokritou
Kee Woei Ng
Yong Qian
Sunil S. Adav
David C. Christiani
Qing Ye
Treye A. Thomas
Sipeng Shen
Sanjay H. Chotirmall
Tuang Yeow Poh
AuthorAffiliation 5 Singapore Phenome Centre, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore; tham_wk@ntu.edu.sg (W.K.T.); ssadav@ntu.edu.sg (S.S.A.)
4 Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA; woe7@cdc.gov (M.T.F.); yaq2@cdc.gov (Y.Q.)
8 Environmental Chemistry and Materials Centre, Nanyang Environment & Water Research Institute, Singapore 637141, Singapore
3 Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA; svp097@mail.harvard.edu (S.P.); kwng@ntu.edu.sg (K.W.N.); pdemokri@hsph.harvard.edu (P.D.)
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; ywei@njmu.edu.cn
9 Office of Hazard Identification an
AuthorAffiliation_xml – name: 3 Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA; svp097@mail.harvard.edu (S.P.); kwng@ntu.edu.sg (K.W.N.); pdemokri@hsph.harvard.edu (P.D.)
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https://www.ncbi.nlm.nih.gov/pubmed/31888290$$D View this record in MEDLINE/PubMed
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2019 by the authors. 2019
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Issue 24
Keywords inhalation
nanotoxicity
metabolomics
biomarkers
printer emitted nanoparticles
transcriptomics
lipidomics
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Snippet Laser printer-emitted nanoparticles (PEPs) generated from toners during printing represent one of the most common types of life cycle released particulate...
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StartPage 6348
SubjectTerms Air Pollutants
Air Pollutants - analysis
Animals
Biomarkers
Cardiovascular disease
Cell division
Diabetes
Disease
Disease - genetics
Gene expression
inhalation
Inhalation Exposure
Inhalation Exposure - adverse effects
Integrated approach
Laser printers
Lipidomics
Lung
Lung - metabolism
Male
Medicine [Science]
Metabolism
metabolomics
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
Nanoparticles
Nanoparticles - adverse effects
Nanotechnology
nanotoxicity
Printer Emitted Nanoparticles
Printing
Rats, Sprague-Dawley
Risk Factors
RNA, Messenger
RNA, Messenger - genetics
RNA, Messenger - metabolism
Rodents
Science::Medicine
Serum
Serum - metabolism
Surveillance
Toxicology
Transcriptome
Transcriptome - genetics
transcriptomics
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Title Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling in Rat Lung, Blood, and Serum for Assessment of Laser Printer-Emitted Nanoparticle Inhalation Exposure-Induced Disease Risks
URI https://cir.nii.ac.jp/crid/1872835442511324928
https://www.ncbi.nlm.nih.gov/pubmed/31888290
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https://pubmed.ncbi.nlm.nih.gov/PMC6940784
Volume 20
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