The cytochrome P-450 isoenzyme CYP2E1 in the biological processing of industrial chemicals: consequences for occupational and environmental medicine

Bolt, H. M., Roos, P. H. and Thier, R. (2003) The cytochrome P-450 isoenzyme CYP2E1 in the biological processing of industrial chemicals: consequences for occupational and environmental medicine. International Archives of Occupational And Environmental Health, 76 3: 174-185. doi:10.1007/s00420-002-0407-4


Author Bolt, H. M.
Roos, P. H.
Thier, R.
Title The cytochrome P-450 isoenzyme CYP2E1 in the biological processing of industrial chemicals: consequences for occupational and environmental medicine
Journal name International Archives of Occupational And Environmental Health   Check publisher's open access policy
ISSN 0340-0131
Publication date 2003-01-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1007/s00420-002-0407-4
Open Access Status DOI
Volume 76
Issue 3
Start page 174
End page 185
Total pages 12
Place of publication New York
Publisher Springer-Verlag
Language eng
Subject 320201 Allergy
Abstract The importance of the isoform CYP2E1 of the human cytochrome P-450 superfamily of enzymes for occupational and environmental medicine is derived from its unique substrate spectrum that includes a number of highly important high-production chemicals, such as aliphatic and aromatic hydrocarbons, solvents and industrial monomers (i.a. alkanes, alkenes, aromatic and halogenated hydrocarbons). Many polymorphic genes, such as CYP2E1, show considerable differences in allelic distribution between different human populations. The polymorphic nature of the human CYP2E1 gene is significant for inter-individual differences in toxicity of its substrates. Since the substrate spectrum of CYP2E1 includes many compounds of basic relevance to industrial toxicology, a rationale for metabolic interactions of different CYP2E1 substrates is provided. In-depth research into the inter-individual phenotypic differences of human CYP2E1 enzyme activities was enabled by the recognition that the 6-hydroxylation of the drug chlorzoxazone is mediated by CYP2E1. Studies on CYP2E1 phenotyping have pointed to inter-individual variations in enzyme activities. There are consistent ethnic differences in CYP2E1 enzyme expression, mostly demonstrated between European and Japanese populations, which point to a major impact of genetic factors. The most frequently studied genetic polymorphisms are the restriction fragment length polymorphisms PstI/RsaI (mutant allele: CYP2E1*5B) located in the 5'-flanking region of the gene, as well as the DraI polymorphism (mutant allele: CYP2E1*6) located in intron 6. These polymorphisms are partly related, as they form the common allele designated CYP2E1*5A. Striking inter-ethnic differences between Europeans and Asians appear with respect to the frequencies of the CYP2E1*5A allele (only approximately 5% of Europeans are heterozygous, but 37% of Asians are, whilst 6% of Asians are homozygous). Available studies indicate a wide variation in human CYP2E1 expression, which are very likely based on complex gene-environment interactions. Major inter-ethnic differences are apparent on the genotyping and the phenotyping levels. Selected cases are presented where inter-ethnic variations of CYP2E1 may provide likely explanations for unexplained findings concerning industrial chemicals that are CYP2E1 substrates. Possible consequences of differential inter-individual and inter-ethnic susceptibilities are related to individual expressions of clinical symptoms of chemical toxicity, to results of biological monitoring of exposed workers, and to the interpretation of results of epidemiological or molecular-epidemiological studies.
Keyword Public, Environmental & Occupational Health
cytochrome p-450
CYP2E1
industrial chemicals
inter-individual variability
inter-ethnic variability
n-hexane
1,3-butadiene
acrylonitrile
acrylamide
Glutathione-s-transferase
Human-liver
Transcriptional Regulation
Genetic-polymorphism
5'-flanking Region
N-hexane
In-vitro
Interindividual Differences
Chlorzoxazone Metabolism
Ethylene-oxide
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown
Additional Notes This document is a journal review.

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
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Created: Sat, 29 Mar 2008, 01:21:44 EST