mRNAs and miRNAs in whole blood associated with MWCNT-induced lung hyperplasia, fibrosis, and bronchiolo-alveolar adenoma and adenocarcinoma following inhalation exposure in mice

Details

• Personal Author:
  Battelli LA ; Castranova, Vincent ; Chen BT ; Dong C ; Guo NL ; Lowry DT ; McKinney W ; Porter DW ; Qian Y ; Raese R ; Reynolds SH ; Sargent LM ; Talkington B
• Description:
  Inhalation exposure to 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 (i.p.) injection of either the initiator methylcholanthrene (MCA, 10 ug/g BW) or vehicle (corn oil). One week after injections, mice were exposed by inhalation to MWCNT (5 mg/m3, 5 hours/day, 5 days/week) or filtered air (control) for a total of 15 days. At 17 months post-exposure, mice were euthanized and examined for lung pathology, and whole blood was collected and analyzed by microarray for global mRNA and miRNA expression. Numerous mRNAs and miRNAs in the blood were significantly up- or down-regulated in the presence of lung pathology after MCA and/ or MWCNT 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. These miRNAs and mRNAs and their respective regulatory networks may be correlated with MWCNT-induced lung pathology and may potentially serve as biomarkers for the presence of lung pathology following MWCNT exposure. [Description provided by NIOSH]
• Subjects:
  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:
  Adenocarcinomas Alveolar-cells Blood-analysis Blood-sampling Cancer Carbon-compounds Carcinomas Cell-transformation Cellular-reactions DNA-damage Exposure-assessment Exposure-levels Inhalants Laboratory-animals Laboratory-techniques Laboratory-testing Lung-cancer Lung-cells Lung-fibrosis Methyl-compounds Nanotechnology Protein-synthesis Proteins Pulmonary-system-disorders Recombinant-DNA Respiratory-system-disorders Ribonucleic-acids

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  144
• Issue:
  1
• NIOSHTIC Number:
  nn:20045955
• Citation:
  Toxicologist 2015 Mar; 144(1):267
• 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:
  2015
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 54th Annual Meeting and ToxExpo, March 22-26, 2015, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2e81568b3763f8dcdbb4767c70e3a77d3b5f83d6fb0dd595711ec87667380608a5a45cfa4b1a361212cf6897bbe5990f0a3f26e11074ed7bf97a13e7be255dba
• Download URL:
  https://stacks.cdc.gov/view/cdc/201163/cdc_201163_DS1.pdf
• File Type:
  [PDF - 218.95 KB ]