Hepatic and Pulmonary Microsomal Benzene Metabolism in CYP2E1 Knockout Mice

Details

• Personal Author:
  Carlson GP ; Powley MW
• Description:
  Benzene is an occupational and environmental toxicant. The major health concern for humans is acute myelogenous leukemia. To exert its toxic effects, benzene must be metabolized via cytochrome P450. CYP2E1 has been identified as the most important cytochrome, P450 isozyme in hepatic benzene metabolism in mice, rats, and humans. In pulmonary microsomes CYP2E1 and members of the CYP2F subfamily are both significantly involved. In the current study CYP2E1 knockout mice and wild-type controls were used to further examine the cytochrome P450 isozymes involved in metabolism of 24 microM benzene. The results show that CYP2E1 is the most important isozyme in the liver, accounting for 96% of the total hydroxylated metabolite formation. However, in the lung CYP2E1 was responsible for only 45% of the formation of total hydroxylated metabolite. Chemical inhibitors of CYP2E1 and CYP2F2 were used to further examine the contributions of these isozymes to benzene metabolism. The results confirmed the finding that while CYP2E1 is the most important isozyme in the liver, CYP2F2 and CYP2E1 are both significantly involved in the lung. [Description provided by NIOSH]
• Subjects:
  Animals Benzene Energy Metabolism Hazardous Substances Laboratories Liver Lung Diseases Occupational Health Phenol Respiratory Tract Diseases Safety

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• Keywords:
  Animal-studies Benzenes Laboratory-animals Liver-disorders Lung-disorders Metabolism Metabolites Phenols Pulmonary-system-disorders Toxic-effects Toxins

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• ISSN:
  0300-483X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Indiana ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  187-194
• Volume:
  169
• Issue:
  3
• NIOSHTIC Number:
  nn:20031159
• Citation:
  Toxicology 2001 Dec; 169(3):187-194
• Contact Point Address:
  School of Health Sciences, 1338 Civil Engineering Building, Purdue University, West Lafayette, IN 47907-1338, USA
• Email:
  gcarlson@purdue.edu
• Federal Fiscal Year:
  2002
• Performing Organization:
  Purdue University, School of Health Sciences, West Lafayette, Indiana
• Peer Reviewed:
  True
• Start Date:
  20010701
• Source Full Name:
  Toxicology
• End Date:
  20270630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:63c8ed0c50a48e988128d7972a629b3fcda033a75afe8709738524a8a9f56aa859566b0eb914cf687d4e3694da496ca8c53d8ef269633700b157a8d79b813230
• Download URL:
  https://stacks.cdc.gov/view/cdc/191494/cdc_191494_DS1.pdf
• File Type:
  [PDF - 86.31 KB ]