Multi-walled carbon nanotube-induced gene expression in the mouse lung: Association with lung pathology

Journal Article · Mon Aug 15 04:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.05.012· OSTI ID:21587812

Pacurari, M ^[1]; Qian, Y ^[2]; Porter, D W; Wolfarth, M ^[2]; Wan, Y; Luo, D ^[1]; Ding, M ^[2]; Castranova, V ^[1]

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1. Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506-9300 (United States)
2. Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States)

Due to the fibrous shape and durability of multi-walled carbon nanotubes (MWCNT), concerns regarding their potential for producing environmental and human health risks, including carcinogenesis, have been raised. This study sought to investigate how previously identified lung cancer prognostic biomarkers and the related cancer signaling pathways are affected in the mouse lung following pharyngeal aspiration of well-dispersed MWCNT. A total of 63 identified lung cancer prognostic biomarker genes and major signaling biomarker genes were analyzed in mouse lungs (n = 80) exposed to 0, 10, 20, 40, or 80 {mu}g of MWCNT by pharyngeal aspiration at 7 and 56 days post-exposure using quantitative PCR assays. At 7 and 56 days post-exposure, a set of 7 genes and a set of 11 genes, respectively, showed differential expression in the lungs of mice exposed to MWCNT vs. the control group. Additionally, these significant genes could separate the control group from the treated group over the time series in a hierarchical gene clustering analysis. Furthermore, 4 genes from these two sets of significant genes, coiled-coil domain containing-99 (Ccdc99), muscle segment homeobox gene-2 (Msx2), nitric oxide synthase-2 (Nos2), and wingless-type inhibitory factor-1 (Wif1), showed significant mRNA expression perturbations at both time points. It was also found that the expression changes of these 4 overlapping genes at 7 days post-exposure were attenuated at 56 days post-exposure. Ingenuity Pathway Analysis (IPA) found that several carcinogenic-related signaling pathways and carcinogenesis itself were associated with both the 7 and 11 gene signatures. Taken together, this study identifies that MWCNT exposure affects a subset of lung cancer biomarkers in mouse lungs. - Research Highlights: > Multi-Walled Carbon Nanotubes affect lung cancer biomarkers in mouse lungs. > The results suggest potentially harmful effects of MWCNT exposure on human lungs. > The results could potentially be used for the medical surveillance of workers.

• OSTI ID: 21587812
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 255; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMALS
BIOLOGICAL MARKERS
BODY
CARBON
CARCINOGENESIS
CARCINOGENS
CHALCOGENIDES
CONTROL
DISEASES
ELEMENTS
GENE AMPLIFICATION
GENES
HAZARDS
LUNGS
MAMMALS
MEDICAL SURVEILLANCE
MESSENGER-RNA
MICE
MUSCLES
NANOSTRUCTURES
NANOTUBES
NEOPLASMS
NETWORK ANALYSIS
NITRIC OXIDE
NITROGEN COMPOUNDS
NITROGEN OXIDES
NONMETALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDES
OXYGEN COMPOUNDS
PATHOGENESIS
PATHOLOGY
POLYMERASE CHAIN REACTION
PUBLIC HEALTH
RESPIRATORY SYSTEM
RNA
RODENTS
VERTEBRATES