Fluoranthene metabolism: human and rat liver microsomes display different stereoselective formation of the trans-2,3-dihydrodiol. 1992

B W Day, and Y Sahali, and D A Hutchins, and M Wildschütte, and R Pastorelli, and T T Nguyen, and S Naylor, and P L Skipper, and J S Wishnok, and S R Tannenbaum
Department of Environmental & Occupational Health, University of Pittsburgh, Pennsylvania 15238.

The metabolism of the environmental carcinogen fluoroanthene by human liver microsomes was compared to that by liver microsomes from rats treated with Aroclor 1254. Although the human-derived system gave primarily one product, similar metabolites were noted from each system. Enantiomers of the major metabolic product, in both cases the trans-2,3-dihydrodiol, were separated by chiral stationary-phase chromatography. Absolute configurations were assigned by application of the benzoate exciton chirality rules to the CD spectra of the 4-(dimethylamino)benzoyl esters. Liver microsomes from Aroclor 1254-treated rats produced the R,R enantiomer of the diol in 75-78% enantiomeric excess, while human liver microsomes produced this enantiomer in only 6-12% excess. The activities of these enantiomers were compared in Salmonella typhimurium strain TM677 mutagenicity assays employing the 9000g supernatant of Aroclor 1254-induced rat liver homogenates. Both the syn- and anti-2,3-dihydrodiol 1,10b-epoxides, which had only been inferred to be metabolites in previous studies, were isolated from the microsomal incubations by preparative reverse-phase HPLC. The evident exceptional aqueous stabilities of these diol epoxides were further examined by half-life determination experiments. Their tetrahydrotetrol hydrolysis products were also noted in the metabolite HPLC profiles. The structures of the tetrahydrotetrols were confirmed by total synthesis.

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
D008968 Molecular Conformation The characteristic three-dimensional shape of a molecule. Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D009152 Mutagenicity Tests Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests. Genetic Toxicity Tests,Genotoxicity Tests,Mutagen Screening,Tests, Genetic Toxicity,Toxicity Tests, Genetic,Genetic Toxicity Test,Genotoxicity Test,Mutagen Screenings,Mutagenicity Test,Screening, Mutagen,Screenings, Mutagen,Test, Genotoxicity,Tests, Genotoxicity,Toxicity Test, Genetic
D002274 Carcinogens, Environmental Carcinogenic substances that are found in the environment. Environmental Carcinogens
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
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
D005449 Fluorenes A family of diphenylenemethane derivatives.
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
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

B W Day, and Y Sahali, and D A Hutchins, and M Wildschütte, and R Pastorelli, and T T Nguyen, and S Naylor, and P L Skipper, and J S Wishnok, and S R Tannenbaum
December 1982, Biochemical and biophysical research communications,
B W Day, and Y Sahali, and D A Hutchins, and M Wildschütte, and R Pastorelli, and T T Nguyen, and S Naylor, and P L Skipper, and J S Wishnok, and S R Tannenbaum
August 1983, Carcinogenesis,
B W Day, and Y Sahali, and D A Hutchins, and M Wildschütte, and R Pastorelli, and T T Nguyen, and S Naylor, and P L Skipper, and J S Wishnok, and S R Tannenbaum
January 1984, Journal of toxicology and environmental health,
B W Day, and Y Sahali, and D A Hutchins, and M Wildschütte, and R Pastorelli, and T T Nguyen, and S Naylor, and P L Skipper, and J S Wishnok, and S R Tannenbaum
January 1992, Chemical research in toxicology,
B W Day, and Y Sahali, and D A Hutchins, and M Wildschütte, and R Pastorelli, and T T Nguyen, and S Naylor, and P L Skipper, and J S Wishnok, and S R Tannenbaum
July 1985, Molecular pharmacology,
B W Day, and Y Sahali, and D A Hutchins, and M Wildschütte, and R Pastorelli, and T T Nguyen, and S Naylor, and P L Skipper, and J S Wishnok, and S R Tannenbaum
February 2000, The Journal of pharmacy and pharmacology,
B W Day, and Y Sahali, and D A Hutchins, and M Wildschütte, and R Pastorelli, and T T Nguyen, and S Naylor, and P L Skipper, and J S Wishnok, and S R Tannenbaum
January 2003, Acta pharmacologica Sinica,
B W Day, and Y Sahali, and D A Hutchins, and M Wildschütte, and R Pastorelli, and T T Nguyen, and S Naylor, and P L Skipper, and J S Wishnok, and S R Tannenbaum
January 1991, Drug metabolism and disposition: the biological fate of chemicals,
B W Day, and Y Sahali, and D A Hutchins, and M Wildschütte, and R Pastorelli, and T T Nguyen, and S Naylor, and P L Skipper, and J S Wishnok, and S R Tannenbaum
May 2012, Chirality,
B W Day, and Y Sahali, and D A Hutchins, and M Wildschütte, and R Pastorelli, and T T Nguyen, and S Naylor, and P L Skipper, and J S Wishnok, and S R Tannenbaum
May 1996, Drug metabolism and disposition: the biological fate of chemicals,
Copied contents to your clipboard!