Polycyclic aromatic hydrocarbon (PAH) o-quinones are products of the dihydrodiol dehydrogenase-catalyzed oxidation of trans-dihydrodiols which are proximate carcinogens. The PAH o-quinones are highly reactive molecules and have the potential to alkylate DNA. In this study, the reactivity of [H-3](+/-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene ([H-3] (+/-)-anti-BPDE), [H-3]benzo[a]pyrene-7,8-dione ([H-3]BPQ) and [H-3](+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a] pyrene ([H-3](+/-)-B[a]P-diol) with DNA were compared. (+/-)-anti-BPDE reacted equally well with native, deproteinated and deproteinated/sheared calf thymus DNA. In each case DNA adducts were formed which upon digestion to deoxyribonucleosides comigrated on reverse-phase (RP)HPLC with adducts synthesized by reacting (+ / -)-anti-BPDE with oligo-p(dG)10. (+/-)-anti-BPDE also reacted with plasmid (pGEM-3) DNA to yield multiple adducts one of which comigrated with the (+)-anti-BPDE - deoxyguanosine adduct. Under identical conditions [H-3]BPQ reacted preferentially with native calf thymus DNA but displayed low reactivity with deproteinated and deproteinated/sheared calf thymus DNA. RP-HPLC analysis of deoxyribonucleoside-BPQ adducts indicated that the predominant adduct formed comigrated with a standard synthesized by reacting BPQ with oligo-p(dG)10. BPQ also reacted with pGEM-3 DNA to yield multiple adducts one of which comigrated with the BPQ-deoxyguanosine adduct. Reactions between [H-3]BPQ and poly(dA), poly(dT), poly(dC) and oligo-p(dG)10 indicated that BPQ preferentially formed deoxyguanosine adducts. In this study, [H-3]BPQ and [H-3](+/-)-anti-BPDE covalently labeled native calf thymus DNA to an equal extent, however, less [H-3]BPQ was recovered as deoxyguanosine adducts. By contrast, no covalent modification of calf thymus DNA, pGEM-3 DNA or oligonucleotides was observed with [H-3](+/-)-B[a]P-diol. These studies indicate that BPQ has the potential to be genotoxic in vitro; that reactivity is heightened in the presence of protein or circular DNA and that the major adduct formed is a deoxyguanosine adduct.
