Characterization of Pulmonary Responses in Mice to Asbestos/Asbestiform Fibers Using Gene Expression Profiles

Details

• Personal Author:
  Gutkin DW ; Harper M ; Kisin ER ; Shurin MR ; Shvedova AA ; Yanamala N
• Description:
  Humans exposed to asbestos and/or asbestiform fibers are at high risk of developing many lung diseases including asbestosis, lung cancer, and malignant mesothelioma. However, the disease-causing potential and specific metabolic mechanisms and pathways associated with various asbestos/asbestiform fiber exposures triggering different carcinogenic and non-carcinogenic outcomes are still largely unknown. The aim of this this study was to investigate gene expression profiles and inflammatory responses to different asbestos/asbestiform fibers at the acute/sub-acute phase that may be related to delayed pathological outcomes observed at later time points. Mice were exposed to asbestos (crocidolite, tremolite asbestos), asbestiform fibers (erionite), and a low pathogenicity mineral fiber (wollastonite) using oropharyngeal aspiration. Similarities in inflammatory and tissue damage responses, albeit with quantitative differences, were observed at day 1 and 7 post treatment. Exposure to different fibers induced significant changes in regulation and release of a number of inflammatory cytokines/chemokines. Comparative analysis of changes in gene regulation in the lung on day 7 post exposure were interpretable in the context of differential biological responses that were consistent with histopathological findings at days 7 and 56 post treatment. Our results noted differences in the magnitudes of pulmonary responses and gene regulation consistent with pathological alterations induced by exposures to four asbestos/asbestiform fibers examined. Further comparative mechanistic studies linking early responses with the long-term endpoints may be instrumental to understanding triggering mechanisms underlying pulmonary carcinogenesis, that is lung cancer versus mesothelioma. [Description provided by NIOSH]
• Subjects:
  Asbestos Immune System Inorganic Chemicals Laboratories Lung Diseases Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Asbestos Fibers Asbestosis Cytokines Gene Expression Histopathology Immune Reaction Laboratory Animals Lung Disease Tissue Culture
• ISSN:
  1528-7394
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Florida ; OSHA Region 3 ; OSHA Region 4 ; Pennsylvania ; 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:
  60-79
• Volume:
  81
• Issue:
  4
• NIOSHTIC Number:
  nn:20050764
• Citation:
  J Toxicol Environ Health A 2018 Feb; 81(4):60-79
• Contact Point Address:
  Anna A. Shvedova, Exposure Assessment Branch, NIOSH, (MS-3030), 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  ats1@cdc.gov
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Mining
• 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-512:2a1d9b243902558f46cfbf7b890b7d409f5b257a639195e5c216485178c2115868b04d456f7dffcafc58f3c2bcda3218ad980d9ea293fa97eb6f4fa1f862f366
• Download URL:
  https://stacks.cdc.gov/view/cdc/210987/cdc_210987_DS1.pdf
• File Type:
  [PDF - 2.09 MB ]