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Hepatic and pulmonary microsomal benzene metabolism in CYP2E1 knockout mice.

Authors
Powley-MW; Carlson-GP
Source
Toxicology 2001 Dec; 169(3):187-194
NIOSHTIC No.
20031159
Abstract
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.
Keywords
Benzenes; Metabolism; Metabolites; Toxins; Toxic-effects; Lung-disorders; Liver-disorders; Pulmonary-system-disorders; Phenols; Laboratory-animals; Animals; Animal-studies
Contact
School of Health Sciences, 1338 Civil Engineering Building, Purdue University, West Lafayette, IN 47907-1338, USA
CODEN
TXCYAC
Publication Date
20011228
Document Type
Journal Article
Email Address
gcarlson@purdue.edu
Funding Type
Grant
Fiscal Year
2002
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-T01-OH-008615
Issue of Publication
3
ISSN
0300-483X
Source Name
Toxicology
State
IN
Performing Organization
Purdue University, School of Health Sciences, West Lafayette, Indiana
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