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

Journal Article · Sun Nov 01 00:00:00 EST 1992 · Chemical Research in Toxicology; (United States)

DOI:https://doi.org/10.1021/tx00030a008· OSTI ID:6696984

Day, B W; Sahali, Y; Hutchins, D A; Wildschuette, M P; Pastorelli, R; Nguyen, T T; Naylor, S; Skipper, P L; Wishnok, J S; Tannenbaum, S R ^[1]

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1. Univ. of Pittsburgh, PA (United States)

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.

• OSTI ID: 6696984
• Journal Information: Chemical Research in Toxicology; (United States), Vol. 5:6, Issue 6; ISSN 0893-228X
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
CARCINOGENS
BIOLOGICAL EFFECTS
FLUORATES
METABOLISM
RATS
CHIRALITY
CHROMATOGRAPHY
EPOXIDES
ESTERS
HALF-LIFE
HOMOGENATES
HUMAN POPULATIONS
HYDROLYSIS
LIVER
METABOLITES
MICROSOMES
SALMONELLA TYPHIMURIUM
SPECTRA
ANIMALS
BACTERIA
BODY
CELL CONSTITUENTS
CHEMICAL REACTIONS
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
DIGESTIVE SYSTEM
FLUORINE COMPOUNDS
GLANDS
HALOGEN COMPOUNDS
ISOTOPES
LYSIS
MAMMALS
MICROORGANISMS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PARTICLE PROPERTIES
POPULATIONS
RADIOISOTOPES
RIBOSOMES
RODENTS
SALMONELLA
SEPARATION PROCESSES
SOLVOLYSIS
VERTEBRATES
YEARS LIVING RADIOISOTOPES
550500* - Metabolism
560300 - Chemicals Metabolism & Toxicology