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.
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 µg 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.
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA.
Brandi N
BN
Snyder-Talkington
Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV, 26506-9300, USA.
Chunlin
C
Dong
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA.
Linda M
LM
Sargent
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA.
Dale W
DW
Porter
WIL Research, Hillsborough, NC, 27278, USA.
Lauren M
LM
Staska
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA.
Ann F
AF
Hubbs
Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV, 26506-9300, USA.
Rebecca
R
Raese
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA.
Walter
W
McKinney
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA.
Bean T
BT
Chen
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA.
Lori
L
Battelli
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA.
David T
DT
Lowry
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA.
Steven H
SH
Reynolds
Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV, 26506, USA.
Vincent
V
Castranova
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA.
Yong
Y
Qian
Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV, 26506-9300, USA.
Nancy L
NL
Guo
D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000236:Adenoma / Q000235:genetics*; D000818:Animals; D053263:Gene Regulatory Networks; D006965:Hyperplasia; D019570:Inhalation Exposure; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000097:blood*; D037742:Nanotubes, Carbon / Q000633:toxicity*; D011658:Pulmonary Fibrosis / Q000235:genetics*; D012333:RNA, Messenger / Q000097:blood*
D035683:MicroRNAs; D037742:Nanotubes, Carbon; D012333:RNA, Messenger
MCA; MWCNT; adenocarcinoma; fibrosis; mRNA; miRNA