Hydrolysis of benzo[a]pyrene diol epoxide and its covalent binding to DNA proceed through similar rate-determining steps.
- 1 May 1984
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 81 (9) , 2635-2639
- https://doi.org/10.1073/pnas.81.9.2635
Abstract
The mutagenic and carcinogenic metabolite of benzo[a]pyrene, (7R,8S)-dihydroxy-(9R,10R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, undergoes 2 major reactions in the presence of [calf] DNA: hydrolysis and covalent binding. Hydrolysis and covalent binding are specific and general acid-catalyzed reactions with the same or similar rate-determining steps. To account for the similarity of rate-determining steps in covalent binding and hydrolysis, 2 models were proposed and tested. In each model, the rate-determining step results in formation of a carbonium ion, which serves as a precursor for both tetrol and adduct. In model A the carbonium ion is partitioned between 2 domains (1 and 2), while in model B there is only 1 domain. Measurements of pseudo-1st-order rate constants, product ratios and rate ratios supply model A, while kinetic results are inconsistent with model B. Domain 1 most likely represents activated benzo[a]pyrenes that are intercalated into DNA, while domain 2 hydrocarbons are physically bound to the outside of the DNA helix.This publication has 25 references indexed in Scilit:
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