BIOMAT Database Logo BIOMAT Database Logo

Biochemistry of 1,3-butadiene metabolism and its relevance to 1,3-butadiene-induced carcinogenicity. 1996

A A Elfarra, and R J Krause, and R R Selzer
Department of Comparative Biosciences, University of Wisconsin, Madison 53706-1102, USA.

Recently, the roles of specific P450 isoforms, myeloperoxidase (MPO), GSH-S-transferase and epoxide hydrolase in the metabolism of 1,3-butadiene, and its major oxidative metabolite, butadiene monoxide (BM), were investigated. The results provided evidence for P450s 2A6 and 2E1 being major catalysts of 1,3-butadiene oxidation in human liver microsomes. cDNA-expressed human P450s 2E1, 2A6, and 2C9 catalyzed BM oxidation to meso- and (+/-)-diepoxybutane (DEB), but the rates of BM oxidation in mouse, rat, or human liver microsomes were much lower than the rates of 1,3-butadiene oxidation in these tissues. Human MPO catalyzed 1,3-butadiene oxidation to BM, but MPO incubations with BM did not yield DEB. Rates of BM formation in mouse and human liver microsomes were similar and were nearly 3.4-fold higher than that obtained with rat liver microsomes. However, rat liver epoxide hydrolase activity was nearly 2-fold higher than that of mouse liver microsomes. Rat and mouse liver GSH-S-transferases exhibited similar BM conjugation kinetics, but rats excreted more BM-mercapturic acids compared to mice given low equimolar doses of BM. BM reacted with guanosine and adenosine to yield N7-, N2-, and N1-guanosinyl and N6-adenosinyl adducts, respectively. These results may contribute to a better understanding of the biochemical basis of 1,3-butadiene-induced carcinogenicity.

UI MeSH Term Description Entries
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D009195 Peroxidase A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. Myeloperoxidase,Hemi-Myeloperoxidase,Hemi Myeloperoxidase
D009705 Nucleosides Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed) Nucleoside,Nucleoside Analog,Nucleoside Analogs,Analog, Nucleoside,Analogs, Nucleoside
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D002070 Butadienes Four carbon unsaturated hydrocarbons containing two double bonds. Butadiene Derivative,Butadiene Derivatives,Derivative, Butadiene,Derivatives, Butadiene
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D004852 Epoxy Compounds Organic compounds that include a cyclic ether with three ring atoms in their structure. They are commonly used as precursors for POLYMERS such as EPOXY RESINS. Epoxide,Epoxides,Epoxy Compound,Oxiranes,Compound, Epoxy,Compounds, Epoxy
D005978 Glutathione A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

A A Elfarra, and R J Krause, and R R Selzer
Carcinogenicity of 1,3-butadiene.
April 1993, Environmental health perspectives,
A A Elfarra, and R J Krause, and R R Selzer
Carcinogenicity of 1,3-butadiene.
September 1992, Lancet (London, England),
A A Elfarra, and R J Krause, and R R Selzer
Carcinogenicity of 1,3-butadiene.
October 1992, Lancet (London, England),
A A Elfarra, and R J Krause, and R R Selzer
Carcinogenicity of exposures to 1,3-butadiene.
October 1992, Scandinavian journal of work, environment & health,
A A Elfarra, and R J Krause, and R R Selzer
Biochemistry of nicotine metabolism and its relevance to lung cancer.
January 2021, The Journal of biological chemistry,
A A Elfarra, and R J Krause, and R R Selzer
An unexpected butadiene diolepoxide-mediated genotoxicity implies alternative mechanism for 1,3-butadiene carcinogenicity.
March 2021, Chemosphere,
A A Elfarra, and R J Krause, and R R Selzer
Inhalation toxicity and carcinogenicity of 1,3-butadiene in Sprague-Dawley rats.
June 1990, Environmental health perspectives,
A A Elfarra, and R J Krause, and R R Selzer
1,3-Butadiene: toxicity and carcinogenicity in laboratory animals and in humans.
January 1992, Reviews of environmental contamination and toxicology,
A A Elfarra, and R J Krause, and R R Selzer
Hepatic microsomal metabolism of 1,3-butadiene.
February 1982, Xenobiotica; the fate of foreign compounds in biological systems,
A A Elfarra, and R J Krause, and R R Selzer
Metabolism of 1,3-butadiene: species differences.
October 1996, Toxicology,
Copied contents to your clipboard!