In Vitro Model of the Hepatic Contribution to Lung Epithelial Cell Toxicity Induced by Ethylbenzene, Styrene, and Naphthalene

Details

• Personal Author:
  Ding X ; Kelty JS ; Van Winkle LS
• Description:
  Ethylbenzene (EB), styrene (ST), and naphthalene (NA) cause toxicity in the lung, but this is thought to require metabolic activation by cytochrome P450 monooxygenases (P450s) in either the liver or the lung. We are developing an in vitro approach to determine whether hepatic bioactivation of these aromatic hydrocarbons can contribute to lung toxicity. We hypothesize that hepatic enzymes are capable of escalating lung epithelial cell damage caused by EB, ST, and NA. Airway epithelial cells from either female mouse trachea (MuEC) or the human bronchiolar epithelial cell line, HBE1, were grown and differentiated at the airliquid interface in transwell inserts. Cells were exposed to 5microM or 10microM EB, 5microM or 10microM ST, or 5microM to 3mM NA, in media containing female mouse liver microsomes. Liver microsomes were boiled to inactivate P450s for negative control experiments. Lung epithelial cell toxicity was assessed by measuring cell permeability and cell density. MuEC cells exposed to 10microM EB with liver microsomes present resulted in a 50% decrease in cell density. No significant MuEC cell death occurred with 10microM EB and boiled liver microsomes. The 5microM EB exposure did not result in significant cell death for MuEC cells. MuEC exposed to ST or NA at 5microM and 10microM resulted in no significant cell death with or without active liver microsomes. For a higher dose of NA, 20microM, MuEC cell death was observed, but the extents were similar in the active and boiled microsome groups (approximately 50% decrease in cell density). No significant cell death was detected in HBE1 cells exposed to 5microM to 3mM NA without active liver microsomes present. With the active microsomes present during exposure to 3 and 0.3mM of NA, a significant (20%) drop in HBE1 cell density was detected. Liver microsome-generated EB metabolites are more potent than liver microsome-generated NA or ST metabolites in causing toxicity in the mouse trachea epithelial cells. MuEC, which are primary mouse trachea cells, had apparently greater intrinsic ability to generate toxic NA metabolites, and were more susceptible to NA toxicity, compared to the HBE1 cells. [Description provided by NIOSH]
• Subjects:
  Animals Cells, Cultured Cytotoxins Energy Metabolism Environmental Exposure Hazardous Substances Hydrocarbons Immune System Lung Occupational Health Respiratory System Safety Styrene Toxicology

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• Keywords:
  Analytical Models Aromatic Hydrocarbons Bioactivation Cell Cultures Cell Culture Techniques Cell Damage Cellular Effects Cell Wall Permeability Cytokines Cytotoxic Effects Cytotoxicity Dose Response Ethyl Benzene Exposure Assessment Exposure Levels Hemoproteins Humans Immune Reaction Immune System In Vitro Study Liver Enzymes Liver Function Liver Microsomes Lung Cells Metabolic Activation Metabolites Naphthalene Toxic Effects Toxic Materials

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; New York ; OSHA Region 2 ; OSHA Region 6 ; OSHA Region 9 ; Texas
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  48-49
• Volume:
  162
• Issue:
  1
• NIOSHTIC Number:
  nn:20051171
• Citation:
  Toxicologist 2018 Mar; 162(1):48-49
• CAS Registry Number:
  Ethylbenzene (CAS RN 100-41-4) ; Naphthalene (CAS RN 91-20-3) ; Styrene (CAS RN 100-42-5)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of California - Davis
• Peer Reviewed:
  False
• Start Date:
  20010930
• Source Full Name:
  The Toxicologist. Society of Toxicology 57th Annual Meeting and ToxExpo, March 11-15, 2018, San Antonio, Texas
• End Date:
  20270929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:79705e88f342e9ff276ca5d8c2e1d8de1b40a5e406c3867b655878bf633c62685032f21ab9a92f05108f748cd5bb54caedde1b9c60b27f505665fd46fbab1e28
• Download URL:
  https://stacks.cdc.gov/view/cdc/211263/cdc_211263_DS1.pdf
• File Type:
  [PDF - 850.78 KB ]