The Role of p53 in Silica-Induced Cellular and Molecular Responses Associated with Carcinogenesis

Details

• Personal Author:
  Castranova, Vincent ; Gwinn MR ; Kashon M ; Leonard, Stephen S. ; Lowry DT ; McKinstry K ; Meighan T ; Reynolds SH ; Sargent LM ; Vallyathan V
• Description:
  Crystalline silica (silica), a suspected human carcinogen, produces an increase in reactive oxygen species (ROS) when fractured using mechanical tools used in several occupations. Although ROS has been linked to apoptosis, DNA damage, and carcinogenesis, the role of enhanced ROS production by silica in silica-induced carcinogenesis is not completely understood. The goal of this study was to compare freshly fractured and aged silica-induced molecular alterations in human immortalized/transformed bronchial epithelial cells (BEAS-IIB) and lung cancer cells with altered (H460) or deficient (H1299) p53 expression. Exposure to freshly fractured or aged silica produced divergent cellular responses in certain downstream cellular events, including ROS production, apoptosis, cell cycle and chromosomal changes, and gene expression. ROS production increased significantly following exposure to freshly fractured silica compared to aged silica in BEAS-IIB and H460 cells. Apoptosis showed a comparable enhanced level of induction with freshly fractured or aged silica in both cancer lines with p53 functional changes. p53 protein was present in the BEAS-IIB and was absent in cancer cell lines after silica exposure. Exposure to freshly fractured silica also resulted in a rise in aneuploidy in cancer cells with a significantly greater increase in p53-deficient cells. Cytogenetic analysis demonstrated increased metaphase spreads, chromosome breakage, rearrangements, and endoreduplication in both cancer cells. These results suggest that altered and deficient p53 affects the cellular response to freshly fractured silica exposure, and thereby enhances susceptibility and augments cell proliferation and lung cancer development. [Description provided by NIOSH]
• Subjects:
  Carcinogens Chromosomes Genetics Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Carcinogenesis Carcinogenicity Cell-damage Cell-function Cell-transformation Cellular-function Cellular-reactions Chromosome-damage Chromosome-disorders Genes Lung-cancer

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• 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:
  72
• Issue:
  23
• NIOSHTIC Number:
  nn:20036053
• Citation:
  J Toxicol Environ Health A 2009 Jan; 72(23):1509-1519
• Contact Point Address:
  Val Vallyathan, PhD, 1095 Willowdale Road, Morgantown, WV 26505, USA
• Email:
  vav1@cdc.gov
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2009
• 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-512:49e08fca2b202a7b2ab04763adc3e91bc3febb4c3fd5bdd48c5bfecc9817b5c25f190468763c0c878bf346204fda359dfa8a43b6b19855b9877e219027c9c1e9
• Download URL:
  https://stacks.cdc.gov/view/cdc/187656/cdc_187656_DS1.pdf
• File Type:
  [PDF - 1.24 MB ]