Multiwalled carbon nanotube-induced gene signatures in the mouse lung: potential predictive value for human lung cancer risk and prognosis

Details

• Personal Author:
  Castranova, Vincent ; Denvir J ; Guo NL ; Pacurari M ; Porter DW ; Qian Y ; Wan Y-W ; Wolfarth MG
• Description:
  Concerns over the potential for multiwalled carbon nanotubes (MWCNT) to induce lung carcinogenesis have emerged. This study sought to (1) identify gene expression signatures in the mouse lungs following pharyngeal aspiration of well-dispersed MWCNT and (2) determine if these genes were associated with human lung cancer risk and progression. Genome-wide mRNA expression profiles were analyzed in mouse lungs (n = 160) exposed to 0, 10, 20, 40, or 80 microg of MWCNT by pharyngeal aspiration at 1, 7, 28, and 56 d postexposure. By using pairwise statistical analysis of microarray (SAM) and linear modeling, 24 genes were selected, which have significant changes in at least two time points, have a more than 1.5-fold change at all doses, and are significant in the linear model for the dose or the interaction of time and dose. Additionally, a 38-gene set was identified as related to cancer from 330 genes differentially expressed at d 56 postexposure in functional pathway analysis. Using the expression profiles of the cancer-related gene set in 8 mice at d 56 postexposure to 10 microg of MWCNT, a nearest centroid classification accurately predicts human lung cancer survival with a significant hazard ratio in training set (n = 256) and test set (n = 186). Furthermore, both gene signatures were associated with human lung cancer risk (n = 164) with significant odds ratios. These results may lead to development of a surveillance approach for early detection of lung cancer and prognosis associated with MWCNT in the workplace. [Description provided by NIOSH]
• Subjects:
  Carcinogens Environmental Monitoring Genetics Hazardous Substances Laboratories Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Risk Assessment Safety

  More +
• Keywords:
  Analytical-models Cancer Carcinogenesis Dose-response Exposure-assessment Exposure-levels Genes Genotoxic-effects Humans Laboratory-animals Laboratory-testing Lung-cancer Lung-cells Mathematical-models Nanotechnology Pulmonary-system-disorders Recombinant-DNA Respiratory-system-disorders Risk-analysis Statistical-analysis Toxic-effects

  More +
• ISSN:
  1528-7394
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; 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:
  75
• Issue:
  18
• NIOSHTIC Number:
  nn:20041501
• Citation:
  J Toxicol Environ Health A 2012 Sep; 75(18):1129-1153
• Contact Point Address:
  Yong Qian, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA
• Email:
  yaq2@cdc.gov
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0)
• Federal Fiscal Year:
  2012
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Toxicology and Environmental Health, Part A: Current Issues
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:cba56084a48ea007e0874ef771f4aa4bc24513649e0844fb8539033533929afd6e32a1193c9efc80bce8f7cf6ca8d9005df1360b4687d793ce2c53c9c5b39acf
• Download URL:
  https://stacks.cdc.gov/view/cdc/194055/cdc_194055_DS1.pdf
• File Type:
  [PDF - 3.86 MB ]