Stereoselective formation and hydration of benzo[c]phenanthrene 3,4-and 5,6-epoxide enantiomers by rat liver microsomal enzymes

Polycyclic Aromatic Hydrocarbons: Metabolism, Activation and Tumour Initiation

“…Thus, primary metabolism of the following PAH, in addition to BaP, has led to a detection of. oxides having mainly (~90%), R,S absolute configuration and/or diols having mainly (~90%) R,R absolute configuration: anthracene ( VAN BLADEREN et al 1984, 1985VON TUNGELN and Fu 1986) and its methylated ) and halogenated ) derivatives; BA YANG et al 1985) and its methylated (CHOU and YANG 1979;YANG et al 1985) and halogenated Cmu et al 1984;Fu et al 1985) derivatives; benzo[c]phenanthrene (BcPh) (lTTAH et al 1983;MUSHTAQ and YANG 1987; VAN BLADEREN et al 1987;YANG et al 1987) and 6-fluoro-BcPh (PRASAD et al 1988); halogenated derivatives of BaP BUHLER et al 1983;CHOU and Fu 1984;THAKKER et al 1984;Fu et al 1986); chrysene (NORDQVIST et al 1981;WESTON et al 1985;WEEMS et al 1986) and its methylated derivatives ); 15,16-dihydrocyclopenta[a]phenanthren-17-one and its methylated derivatives (HADFIELD et al 1984;COOMBS and BHATT 1987); dibenz[c,h]acridine (THAKKER et al 1985b); phenanthrene (NORDQVIST et al 1981); and triphenylene (THAKKER et al 1985c. It should be noted that not all the PAH listed here have, as yet, been shown to possess biological activity (see DIPPLE et al 1984).…”

Absolute configurations of K-region epoxide enantiomers of 3-methylcholanthrene, benz[a]anthracene, and benzo[a]pyrene

“…Enantiomeric compositions of some metabolically formed K-region epoxides have been found to be highly dependent on the type of cytochrome P-450 isozymes present in the microsomal enzyme preparations (7)(8)(9)(10)(11). Thus, the stereoheterotopic enzyme-substrate interaction determines the absolute configuration and enantiomeric purity of epoxides formed.…”

“…K-region as well as non-K-region epoxides formed in the metabolism of some PAHs can be stabilized and isolated by normal-phase HPLC (7)(8)(9)(10)(11). Enantiomers of many of these epoxides can be resolved directly by chiral stationary phase (CSP) HPLC (8,9).…”

“…K-region as well as non-K-region epoxides formed in the metabolism of some PAHs can be stabilized and isolated by normal-phase HPLC (7)(8)(9)(10)(11). Enantiomers of many of these epoxides can be resolved directly by chiral stationary phase (CSP) HPLC (8,9). Thus, the enantiomeric composition of many K-region epoxides formed in the metabolism of PAHs by various drug-metabolizing enzyme systems can be determined either directly by CSP HPLC or by CD spectral analysis when the circular dichroism (CD) spectral data of enantiomerically pure epoxides are known (7)(8)(9)(10)(11).…”

“…Enantiomers of many of these epoxides can be resolved directly by chiral stationary phase (CSP) HPLC (8,9). Thus, the enantiomeric composition of many K-region epoxides formed in the metabolism of PAHs by various drug-metabolizing enzyme systems can be determined either directly by CSP HPLC or by CD spectral analysis when the circular dichroism (CD) spectral data of enantiomerically pure epoxides are known (7)(8)(9)(10)(11). However, the exact asymmetric enzyme-substrate interaction requires the knowledge of the absolute configurations of epoxide enantiomers.…”