Biotransformation of trans-4,5-Dihydroxy-4,5-dihydrobenzo[a]pyrene to Benzo[a]pyrene Bis-Diols and DNA Adducts by Induced Rat Liver Microsomes†

The biotransformation of (±)-trans-4,5-dihydroxy-4,5-dihydrobenzo[a]pyrene (trans-B[a]P-4,5-diol), the K-region dihydrodiol of B[a]P, by β-naphthoflavone (BNF)-induced rat liver microsomes was studied. trans-B[a]P-4,5-diol was metabolized to six major products as characterized by NMR, MS, and UV spectroscopy, and all were identified as bis-diols:  two diastereomers of trans,trans-4,5:7,8-tetrahydroxy-4,5:7,8-tetrahydrobenzo[a]pyrene (trans,trans-B[a]P-4,5:7,8-bis-diol), two diastereomers of trans,trans-4,5:9,10-tetrahydroxy-4,5:9,10-tetrahydrobenzo[a]pyrene (trans,trans-B[a]P-4,5:9,10-bis-diol), and two diastereomers of the somewhat unusual trans,trans-1,2:4,5-tetrahydroxy-1,2:4,5-tetrahydrobenzo[a]pyrene (trans,trans-B[a]P-1,2:4,5-bis-diol). BNF-induced rat liver microsomes also metabolized B[a]P to the same trans-B[a]P-4,5-diol-derived bis-diols. The ability of trans-B[a]P-4,5-diol to form DNA adducts was investigated using 32P-postlabeling techniques specifically designed to detect stable polar DNA add...