Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Kinetic factors involved in the metabolism of benzene in mouse lung and liver.

Authors
Sheets-PL; Carlson-GP
Source
J Toxicol Environ Health, A 2004 Mar; 67(5):421-430
NIOSHTIC No.
20031165
Abstract
Benzene is an occupational and environmental toxicant. The main human health concern associated with benzene exposure is acute myelogenous leukemia. Benzene produces lung tumors in mice, while its effects on human lung are not clear. The adverse effects of benzene are dependent on its metabolism by the cytochrome P-450 enzyme system. The isozymes CYP2E1 and CYP2F2 play roles in the metabolism of benzene at low, environmentally relevant concentrations. Previous studies indicate that the mouse lung readily metabolizes benzene and that CYP2F2 plays a role in this biotransformation. The significance of CYP2E1 and CYP2F2 in benzene metabolism was determined by measuring their apparent kinetic parameters K(m) and V(max). Use of wild-type and CYP2E1 knockout mice and selective inhibitors allowed the determination of the individual importance of both CYP2E1 and CYP2F2 in mouse liver and lung. A simple Michaelis-Menten relationship involving Lineweaver-Burk plots for the microsomal metabolism of benzene shows the apparent kinetic factors are different between the wild-type (K(m): 30.4 microM, V(max): 25.3 pmol/mg protein/min) and knockout (K(m): 1.9 microM, V(max): 0.5 pmol/mg protein/min) mouse livers. Wild-type lung has a K(m) of 2.3 microM and V(max) of 0.9 pmol/mg protein/min. CYP2E1 knockout lung has similar affinity and metabolic activity with a K(m) of 3.7 microM and V(max) of 1.2 pmol/mg protein/min. These data suggest CYP2E1 is less important in the lung than liver, and that it has a lower affinity for benzene but higher rate of hydroxylated metabolite production than does CYP2F2, which plays the predominant role in metabolizing benzene in mouse lung.
Keywords
Environmental-health; Toxicology; Toxins; Toxic-effects; Metabolism; Benzenes; Lung; Lung-disorders; Liver; Liver-disorders; Pulmonary-system-disorders; Occupational-health; Occupational-hazards; Environmental-hazards; Laboratory-animals; Animals; Animal-studies
CODEN
JTEHD6
CAS No.
71-43-2
Publication Date
20040312
Document Type
Journal Article
Email Address
frank@purdue.edu
Funding Type
Grant
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-T01-OH-008615
Issue of Publication
5
ISSN
1528-7394
Source Name
Journal of Toxicology and Environmental Health, Part A: Current Issues
State
IN
Performing Organization
Purdue University, School of Health Sciences, West Lafayette, Indiana
TOP