Metabolic and stereoselective formations of non-K-region benz[a]anthracene 8,9- and 10,11-epoxides

Stereoselective formation and hydration of 12-methylbenz[a]anthracene 5,6-epoxide enantiomers by rat liver microsomal enzymes

“…By using the organic base triethylamine in the solvents for extraction and h.p.l.c. elution, we have successfully isolated K-region as well as non-K-region epoxides formed in the metabolisms of benzo [a]pyrene (Yang & Chiu, 1985), BA (Yang & Chiu, 1985;Mushtaq et al, 1986) and, in the present study, 12-MBA. Since the enantiomers of K-region epoxides can be directly separated by c.s.p.-h.p.l.c.…”

“…The enantiomers of 8,9-epoxide and of 10,1 1-epoxide were not separated by the ionically bonded (S)-DNBL column. The identities of the metabolically formed 5,6-, 8,9-and 10,11 -epoxides were established by u.v.-visibleregion absorption and mass-spectral analyses similar to those described previously (Mushtaq et at., 1986). Furthermore, when each metabolically formed epoxide was incubated with liver microsomes from PB-treated rats in the absence of NADPH, a corresponding trans-dihydrodiol was obtained.…”

“…The procedure is similar to that described previously (Mushtaq et al, 1986). A 150 ml reaction mixture contained 150 mg protein equivalent of rat liver microsomes, 7.5 mmol of Tris/HCl (pH 7.5), 0.45 mmol of MgCl2, 15 units of glucose-6-phosphate dehydrogenase, 15 mg of NADP+, 96 mg of glucose 6-phosphate and 0.09 mmol ofthe microsomal epoxide hydrolase inhibitor TCPO.…”

“…(Fig. 4) on-a silica-gel column with an elution solvent containing ethyl acetate, hexane and triethylamine as previously described (Mushtaq et al, 1986). 12-MBA 5,6-epoxide (peak 2 of Fig.…”

The Quantitative Structure-Mutagenicity Relationship of Polycylic Aromatic Hydrocarbon Metabolites

“…Benz [a]anthracene (BA) and its metabolitic products which are metabolically activated and are both mutagenic and carcinogenic polycyclic aromatic compounds (PAH) include BA-oxides, -phenols, -quinones, -dihydrodiols and -diolepoxides [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Although the mutagenicity of these metabolites has been demonstrated repeatedly using short-term tests (STTs), a few dose-response data are available [18][19][20][21][22][23][24][25][26][27][28].…”