mRNAs and miRNAs in whole blood associated with lung hyperplasia, fibrosis, and bronchiolo-alveolar adenoma and adenocarcinoma after multi-walled carbon nanotube inhalation exposure in mice

Details

• Personal Author:
  Battelli L ; Castranova, Vincent ; Chen BT ; Dong C ; Guo NL ; Hubbs, Ann F. ; Lowry DT ; McKinney W ; Porter DW ; Qian Y ; Raese R ; Reynolds SH ; Sargent LM ; Snyder-Talkington BN ; Staska LM
• Description:
  Inhalation exposure to multi-walled carbon nanotubes (MWCNT) in mice results in inflammation, fibrosis and the promotion of lung adenocarcinoma; however, the molecular basis behind these pathologies is unknown. This study determined global mRNA and miRNA profiles in whole blood from mice exposed by inhalation to MWCNT that correlated with the presence of lung hyperplasia, fibrosis, and bronchiolo-alveolar adenoma and adenocarcinoma. Six-week-old, male, B6C3F1 mice received a single intraperitoneal injection of either the DNA-damaging agent methylcholanthrene (MCA, 10 microg g-1 body weight) or vehicle (corn oil). One week after injections, mice were exposed by inhalation to MWCNT (5 mg m-3, 5 hours per day, 5 days per week) or filtered air (control) for a total of 15 days. At 17 months post-exposure, mice were euthanized and examined for the development of pathological changes in the lung, and whole blood was collected and analyzed using microarray analysis for global mRNA and miRNA expression. Numerous mRNAs and miRNAs in the blood were significantly up- or down-regulated in animals developing pathological changes in the lung after MCA/corn oil administration followed by MWCNT/air inhalation, including fcrl5 and miR-122-5p in the presence of hyperplasia, mthfd2 and miR-206-3p in the presence of fibrosis, fam178a and miR-130a-3p in the presence of bronchiolo-alveolar adenoma, and il7r and miR-210-3p in the presence of bronchiolo-alveolar adenocarcinoma, among others. The changes in miRNA and mRNA expression, and their respective regulatory networks, identified in this study may potentially serve as blood biomarkers for MWCNT-induced lung pathological changes. [Description provided by NIOSH]
• Subjects:
  Biological Assay Biomarkers DNA Environmental Monitoring Hematologic Tests Inhalation Exposure Laboratories Lung Lung Diseases Neoplasms Occupational Health Pathology Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Adenocarcinoma Adenocarcinomas Alveolar-cells Author Keywords: MRNA Bioassays Blood-analysis Blood-sampling Cancer Carbon-compounds Carcinomas Cell-transformation Cellular-reactions DNA-damage Exposure-assessment Exposure-levels Fibrosis Inhalants Laboratory-animals Laboratory-techniques Laboratory-testing Lung-cancer Lung-cells Lung-fibrosis MCA Methyl-compounds MiRNA MWCNT Nanotechnology Protein-synthesis Proteins Pulmonary-system-disorders Recombinant-DNA Respiratory-system-disorders Ribonucleic-acids

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• ISSN:
  0260-437X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 3 ; OSHA Region 4 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  161-174
• Volume:
  36
• Issue:
  1
• NIOSHTIC Number:
  nn:20046211
• Citation:
  J Appl Toxicol 2016 Jan; 36(1):161-174
• Contact Point Address:
  Yong Qian, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505-2888, USA
• Email:
  yaq2@cdc.gov
• CAS Registry Number:
  3-Methylcholanthrene (CAS RN 56-49-5) ; Carbon (CAS RN 7440-44-0) ; Graphene (CAS RN 1034343-98-0)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Applied Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8d157da7d48ae7c0e0e7031a4bc874a68a22f129eb00dc18c243aa2d2f9344851e6fbde3c78abfb2593bdeeaf6f32514e8cffb6a4478196555573edf07669f7e
• Download URL:
  https://stacks.cdc.gov/view/cdc/201334/cdc_201334_DS1.pdf
• File Type:
  [PDF - 401.08 KB ]