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Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects
Abstract
The role of human cytochrome P-450 IIE1 (P-450 IIE1) in the oxidation of a number of suspect carcinogens was examined by using a variety of approaches, including (1) selective inhibition of catalytic activity in human liver microsomes by diethyldithiocarbamate, which was found to be a selective mechanism-based inactivator of P-450 IIE1, (2) correlation of rates of different catalytic activities with each other and with chlorzoxazone 6-hydroxylation, an indicator of P-450 IIE1, in human liver microsomes, (3) demonstration of catalytic activity in reconstituted systems containing purified human P-450 IIE1, and (4) immunoinhibition of catalytic activity in human liver microsomes with rabbit anti-human P-450 IIE1. The results collectively indicate that P-450 IIE1 is a major catalyst of the oxidation of benzene, styrene, CCl4, CHCl3, CH2Cl2, CH3Cl, CH3CCl3, 1,2-dichloropropane, ethylene dichloride, ethylene dibromide, vinyl chloride, vinyl bromide, acrylonitrile, vinyl carbamate, ethyl carbamate, and trichloroethylene. Levels of P-450 IIE1 can vary considerably among individual humans--the availability of chlorzoxazone as a noninvasive probe of human P-450 IIE1 and of disulfiram (oxidized diethyldithiocarbamate) as an inhibitor may facilitate discernment of the in vivo significance of human P-450 IIE1 as a factor in the bioactivation and detoxication of these cancer suspects. Further, many investigations with diethyldithiocarbamate, disulfiram, and ethanol in humans and experimental animals may be interpreted in light of mechanisms involving P-450 IIE1.
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Citations
Cited by
Mirvish, S. S. (1995) · Cancer Letters · doi:10.1016/0304-3835(95)03786-v · Cited by 916
Role of cytochromes P450 in chemical toxicity and oxidative stress: studies with CYP2E1
Gonzalez, F. J. (2005) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2004.04.021 · Cited by 555
Cantor, K. P., Villanueva, C. M., Silverman, D. T., Figueroa, J. D., Real, F. X., Garcia-Closas, M., Malats, N., Chanock, S., Yeager, M., Tardon, A., et al. (2010) · Environmental Health Perspectives · doi:10.1289/ehp.1002206 · Cited by 238
Identification of Human Liver Cytochrome P450 Isoforms Mediating Omeprazole Metabolism
ANDERSSON, T., MINERS, J. O., VERONESE, M. E., TASSANEEYAKUL, W., TASSANEEYAKUL, W., MEYER, U. A., & BIRKETT, D. J. (1993) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.1993.tb00410.x · Cited by 230
Andersson, T., Miners, J., Veronese, M., & Birkett, D. (1994) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.1994.tb04336.x · Cited by 225
Metadata
- Authors
- Guengerich, F. P., Kim, D. H., & Iwasaki, M.
- Venue
- Chemical Research in Toxicology
- Publisher
- American Chemical Society (ACS)
- Published
- 1991-03
- Volume
- 4
- Issue
- 2
- Pages
- 168-179
- ISSN
- 0893-228X (ISSN-L)
- 1520-5010
- OpenAlex
- W1984526747
- Cited by
- 1,169
- References
- 0
- FWCI
- 40.31
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. https://app.cochat.ai/papers/10.1021/tx00020a008
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- Guengerich, F. P., Kim, D. H., & Iwasaki, M. (1991). Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chemical Research in Toxicology. https://doi.org/10.1021/tx00020a008
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
