Influence of Na super(+) on DNA reactions with aromatic epoxides and diol epoxides: Evidence that DNA catalyzes the formation of benzo[a]pyrene and benz[a]anthracene adducts at intercalation sites

Reactions of the benzo[a]pyrene (BP) and benz[a]anthracene (BA) metabolites, ( plus or minus )-trans-7,8-dihydroxy-anti 9,10-epoxy-7,8,9,10-tetrahydro-BP (BPDE), ( plus or minus )-trans-3,4-dihydroxy-anti-1,2-epoxy-1,2,3,4-tetrahydro-BA (BADE), ( plus or minus )-BP-4,5-oxide (BPO), and ( plus or minus )-BA-5,6-oxide (BAO), were examined under pseudo-first-order conditions at varying Na super(+) (2.0-100 mM) and native, calf thymus DNA (ctDNA) concentrations. In 0.2 mM ctDNA and 2.0 mM Na super(+), at a pH of 7.3, most BPDE, BADE, BPO, and BAO (87-95%) undergo DNA catalyzed hydrolysis or rearrangement. For BPDE and BPO, overall, pseudo-first-order rate constants, k, in 2.0 mM Na super(+) and 0.2 mM ctDNA are 21-72 times larger than values obtained without DNA. For BADE and BAO, the rate constants are less strongly influenced by DNA; k values in 0.2 mM ctDNA are only 9-12 times larger than values obtained without DNA. Kinetic data for BPDE, BPO, BADE, and BAO and DNA intercalation association constants (K sub(A)) for BP and BA diols which are model compounds indicate that K sub(A) values for BPDE and BPO in 2.0 mM Na super(+) are 6.6-59 times larger than those of BADE and BAO. The greater DNA enhancement of rate constants for BPDE and BPO, versus BADE and BAO, correlates with the larger K sub(A) values of the BP metabolites. DNA adducts, which account for less than 10% of the yields, also form. For BPDE in 0.20 mM ctDNA, k decreases 5.1 times as the Na super(+) concentration increases from 2.0 to 100 mM. Nevertheless, the DNA adduct level remains constant over the range of Na super(+) concentrations examined. These results provide evidence that, for BPDE in 0.20 mM DNA and 2.0 mM Na super(+), ctDNA adduct formation follows a mechanism which is similar to that for DNA catalyzed hydrolysis. The pseudo-first-order rate constant for adduct formation, k sub(Ad), given approximately by k sub(Ad) approximately (k sub(cat,Ad)K sub(A)[DNA])/(1 + K sub(A)[DNA]), where k sub(cat,Ad) is a catalytic rate constant. For BADE, BPO, and BAO, the influence of varying DNA and Na super(+) concentrations on k values is similar to that for BPDE, and provides evidence that the formation of adducts follows the same rate law.