Rates of hydrolysis and extents of dna binding of 5-methylchrysene dihydrodiol epoxides

Assieh A. Melikian, Joanna M. Leszczynska, Shantu Amin, Stephen S. Hecht, Dietrich Hoffmann, John Pataki, Ronald G. Harvey

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Abstract

The rates of hydrolysis in the absence and presence of native and denatured DNA, and the extents of DNA binding of five dihydrodiol epoxides derived from 5-methylchrysene (5-MeC) and chrysene have been determined. The compounds studied were: trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-MeC; trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-Mec; trans-1,2-dihydroxyyn-3,4-epoxy-1,2,3,4-tetrahydro-5-MeC; frans-7,8-dihydroxy-syn-9,10-epoxy-7,8,9, 10-tetrahydro-5-MeC; and trans-1, 2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahy-drochrysene. In the absence of DNA, at pH 7 and 37°C half-lives of trans-1,2-dihydroxy-syn-3,4-epoxy-1,2,3,4-tetrahydro-5-MeC and trans--1,2-dihydroxy-anti--3,4-epoxy-1,2,3,4-tetrahydro-5-MeC were similar, t1/2 = 62 and 59 min, while trans--7,8-dihydroxy-syn-9,10-epoxy-7,8,9,10-tetrahydro-5-MeC hydrolyzed faster than frans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-MeC, t1/2 = 5.4 versus 17.5 min; trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydrochrysene had the slowest rate of hydrolysis, t1/2 = 104 min. Studies of the effects of native and denatured DNA on the rates of hydrolysis of the dihydrodiol epoxides indicated that native DNA remarkably accelerated these rates for all dihydrodiol epoxides, but the degree of acceleration varied for the different dihydrodiol epoxides. The acceleration of hydrolytic rates by native DNA relative to that by denatured DNA was correlated with the covalent binding of these dihydrodiol epoxides with DNA in vitro. The catalytic effect of DNA in enhancing the rates of hydrolysis of dihydrodiol epoxides and the relative extents of covalent binding of the dihydrodiol epoxides to DNA were in the following order: frans-1,2-dihy-droxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-MeC > frans-7,8-di-hydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-MeC > trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydrochrysene > trans -1,2-dihydroxy-syn-3,4-epoxy-1,2,3,4-tetrahydro-5-MeC > trans -7,8-dihydroxynsyn-9,10-epoxy-7,8,9,10-tetrahydro-5-MeC. The results of this study suggest that physical interactions with DNA are important in determining the relative extents of binding of these dihydrodiol epoxides to DNA in vitro.

Original languageEnglish (US)
Pages (from-to)1990-1996
Number of pages7
JournalCancer Research
Volume45
Issue number5
Publication statusPublished - May 1 1985

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Melikian, A. A., Leszczynska, J. M., Amin, S., Hecht, S. S., Hoffmann, D., Pataki, J., & Harvey, R. G. (1985). Rates of hydrolysis and extents of dna binding of 5-methylchrysene dihydrodiol epoxides. Cancer Research, 45(5), 1990-1996.