Effects of pH and salt concentration on the hydrolysis of a benzo[alpha]pyrene 7,8-diol-9,10-epoxide catalyzed by DNA and polyadenylic acid.
The time-dependent absorbance change that occurs when benzo[alpha]pyrene 7,8-diol-9,10-epoxide is added to solutions of calf thymus DNA has been shown, by an unequivocal chromatographic method, to correspond to DNA-catalyzed hydrolysis of the diol-epoxide. At 25 degrees C and mu = 0.10, the kinetics of the reaction of the diol-epoxide with polyadenylic acid or DNA are consistent with preequilibrium formation of a non-covalent complex between the diol-epoxide and the polynucleotide or DNA, followed by hydrolysis of the bound epoxide by a process that is first-order in hydronium ions. Cacodylic acid also catalyzes the hydrolysis of the epoxide bound to polyadenylic acid. The rate of the DNA-catalyzed hydrolysis exhibits little or no enantiomeric selectivity for the diol-epoxide. DNA catalyzed hydrolysis of the diol-epoxide is extraordinarily sensitive to the salt concentration in the reaction medium: the rate of hydrolysis of the bound epoxide at pH 7 is retarded by a factor of approximately 45 in the presence of 0.1 M sodium chloride compared to a 1 mM buffer containing no added salt. Thus, studies of the interactions of DNA with carcinogenic diol-epoxides must take into account the ionic environment of DNA within the cell.
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D001580:Benzopyrenes; D002384:Catalysis; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D009994:Osmolar Concentration; D011061:Poly A
D001580:Benzopyrenes; D011061:Poly A; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA