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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 May;81(9):2635–2639. doi: 10.1073/pnas.81.9.2635

Hydrolysis of benzo[a]pyrene diol epoxide and its covalent binding to DNA proceed through similar rate-determining steps.

T Meehan, D M Bond
PMCID: PMC345124  PMID: 6425834

Abstract

The mutagenic and carcinogenic metabolite of benzo[a]pyrene, (7R,8S)-dihydroxy-(9R,10R)-epoxy-7,8, 9,10-tetrahydrobenzo[a]pyrene, undergoes two major reactions in the presence of DNA: (i) hydrolysis and (ii) covalent binding. We report that 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 we propose and test two models. 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 two domains (1 and 2), while in model B there is only one domain. Measurements of pseudo-first-order rate constants, product ratios, and rate ratios support 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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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