Gene expression profile of human lung epithelial cells chronically exposed to single-walled carbon nanotubes

Details

• Personal Author:
  Chen D ; Lu Y ; Luanpitpong S ; Rojanasakul Y ; Stueckle, Todd A. ; Wang L
• Description:
  A rapid increase in utility of engineered nanomaterials, including carbon nanotubes (CNTs), has raised a concern over their safety. Based on recent evidence from animal studies, pulmonary exposure of CNTs may lead to nanoparticle accumulation in the deep lung without effective clearance which could interact with local lung cells for a long period of time. Physicochemical similarities of CNTs to asbestos fibers may contribute to their asbestos-like carcinogenic potential after long-term exposure, which has not been well addressed. More studies are needed to identify and predict the carcinogenic potential and mechanisms for promoting their safe use. Our previous study reported a long-term in vitro exposure model for CNT carcinogenicity and showed that 6-month sub-chronic exposure of single-walled carbon nanotubes (SWCNT) causes malignant transformation of human lung epithelial cells. In addition, the transformed cells induced tumor formation in mice and exhibited an apoptosis resistant phenotype, a key characteristic of cancer cells. Although the potential role of p53 in the transformation process was identified, the underlying mechanisms of oncogenesis remain largely undefined. Here, we further examined the gene expression profile by using genome microarrays to profile molecular mechanisms of SWCNT oncogenesis. Based on differentially expressed genes, possible mechanisms of SWCNT-associated apoptosis resistance and oncogenesis were identified, which included activation of pAkt/p53/Bcl-2 signaling axis, increased gene expression of Ras family for cell cycle control, Dsh-mediated Notch 1, and downregulation of apoptotic genes BAX and Noxa. Activated immune responses were among the major changes of biological function. Our findings shed light on potential molecular mechanisms and signaling pathways involved in SWCNT oncogenic potential. [Description provided by NIOSH]
• Subjects:
  Carcinogens Lung Occupational Health Respiratory System Safety
• Keywords:
  Author Keywords: Single-walled Carbon Nanotubes Carcinogenesis Gene Expression Lung Cells Microarray Molecular Biology Nanomaterials P53 Pathways Single-walled Carbon Nanotubes SWCNT

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• ISSN:
  1931-7573
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Alabama ; OSHA Region 3 ; OSHA Region 4 ; 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:
  12
• Volume:
  10
• NIOSHTIC Number:
  nn:20045653
• Citation:
  Nanoscale Res Lett 2015 Jan; 10:12
• Contact Point Address:
  Dongquan Chen, Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294
• Email:
  dongquan@uab.edu
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Nanoscale Research Letters
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7b7f618356868e735a048e7565ddd2e43c623c7bd7ab77c5bec8a95b20b12d76c35491ccbd2c26076c5571ef65682e03587b5d8806f41684b30e782e5958e58d
• Download URL:
  https://stacks.cdc.gov/view/cdc/200999/cdc_200999_DS1.pdf
• File Type:
  [PDF - 1.15 MB ]