Biotransformation and DNA adduct formation of trans-8,9-dihydroxy-8,9-dihydrodibenzo[a,l]pyrene by induced rat liver and human CYP1A1 microsomes

In order to explain the adduct patterns observed from the human CYP1A1-medi ated binding of dibenzo[a,l]pyrene (DB [a,l]P) to DNA, we have investigated the further metabolism and DNA adduct activity of trans-DB [a,l]P-8,9-diol by induced rat liver and human CYP1A1 microsomes. trans-DB[a,l]P-8,9-diol was synthesized and metabolic studies with beta-naphthoflavone-induced rat liver microsomes indicated three major metabolites: 2 diastereomers of tran s, trans-8,9,11,12-tetrahydro-8,9, 11,12-tetrahydroxy-DB [a,l]P and 8,9,13, 14-tetrahydro-8,9,13,14-tetrahydroxy-DB[a,l]P. DB[a,l]P when activated by C YP1A1/epoxide hydrase (EH) and calf thymus DNA gave a complex pattern of DN A adducts most of which cochromatograph with syn- and anti-DB[a,l]P fjord r egion diol epoxide-DNA standards. Two highly polar eluting adducts were als o observed, one which cochromatographs with the single major DNA adduct obt ained from the CYP1A1/EH activation of trans-DB[a,l]P-8,9-diol. The relativ e retention time of this adduct suggests either a bis-diol epoxide adduct o r a more polar diol epoxide adduct.