Identification of novel exposure and lung cancer gene markers in carbon nanotube-exposed human lung epithelial cells

Details

• Personal Author:
  Castranova, Vincent ; Derk R ; Meighan T ; Mishra A ; Rojanasakul Y ; Stueckle, Todd A. ; Wang L
• Description:
  Concern for increased risk of CNT-induced lung cancer has arisen due to asbestos-like high aspect ratio, pulmonary persistence and fibrosis. Our previous study found that chronic in vitro exposure to dispersed single (D-SWCNT) and multi wall CNT (D-MWCNT) resulted in neoplastic transformation in human small airway epithelial cells (SAEC). Genome profiling identified oncogene signaling mechanisms in CNT SAECs that were quite different from asbestos-exposed (ASB) SAEC. Few in vivo studies identified whole lung gene markers associated with MWCNT exposure, but did not compare CNT vs. asbestos genetic response. Here, toxicogenomic profiling with correlation feature selection strategies identified particle-specific, key gene markers from our previous study. D-SWCNT, D-MWCNT, ASB, ultrafine carbon black (UFCB) and control SAEC genome profiles were subjected to comparative marker and class neighbor analyses followed by multistep cross validation to identify genes with highly correlated expression for each treatment. Specific treatment markers and genome profiles were subjected to Ingenuity Pathway and Biomarker Analysis to determine both specific markers performance and identify disease markers. Gene marker subsets and disease markers were validated using rtPCR and protein expression. Here, we present robust SWCNT, MWCNT, ASB and UFCB specific gene marker sets for in vitro chronically exposed SAEC. Matching our original analysis, both D-MWCNT and D-SWCNT markers were associated with lipid metabolism and cancer while ASB and UFCB centered on inflammatory response and senescence, respectively. Biomarker Analysis identified known lung and other cancer markers (MYC, PPARG) in CNT SAECs which differed from inflammation-associated cancer markers (IL-1B) in ASB SAECs. In conclusion, toxicogenomic profiling in a chronic in vitro exposure model identified particle-specific gene markers and known lung cancer markers which can potentially aid in assessing CNT exposure and detection of early disease markers. [Description provided by NIOSH]
• Subjects:
  Biomarkers Energy Metabolism Fibrosis Genetics Lipids Lung Lung Diseases Neoplasms Nervous System Occupational Exposure Occupational Health Respiratory System Respiratory Tract Diseases Safety Toxicology

  More +
• Keywords:
  Biotransformation Cancer Cell-alteration Cellular-reactions Chronic-exposure Gene-mutation Genes Genotoxic-effects In-vitro-studies In-vivo-studies Lung-cancer Lung-fibrosis Metabolism Nanotechnology Neoplastic-transformation Oncogenic-agents Proteins Pulmonary-system-disorders Respiratory-system-disorders

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; OSHA Region 6 ; Texas ; 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:
  91
• Volume:
  132
• Issue:
  1
• NIOSHTIC Number:
  nn:20042390
• Citation:
  Toxicologist 2013 Mar; 132(1):91
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0) ; Carbon black (CAS RN 1333-86-4)
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5a71ab948a638e60de9c205bfc29c06986a0ff8d1dbc88d6180d58a8aca7855fc1f439040bfcb20bf5b40bbf28b637294e5e992e9a71a9a90e81f376ea58b03f
• Download URL:
  https://stacks.cdc.gov/view/cdc/194622/cdc_194622_DS1.pdf
• File Type:
  [PDF - 2.13 MB ]