STUDY OF CHEMICAL CARCINOGENESIS .78. RATES OF HYDROLYSIS AND EXTENTS OF DNA-BINDING OF 5-METHYLCHRYSENE DIHYDRODIOL EPOXIDES

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (5) , 1990-1996
Abstract
The rates of hydrolysis in the absence and presence of native and denatured DNA [from calf thymus] and the extents of DNA binding of 5 dihydrodiol epoxides derived from 5-methylchrysene (5-MeC) and chrysene were 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-dihydroxy-syn-3,4-epoxy-1,2,3,4-tetrahydro-5-MeC; trans-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-tetrahydrochrysene. In the absence of DNA, at pH 7 and 37.degree. C half-lives [t1/2] 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 trans-7,8-dihydroxy-anti-9,19-epoxy-7,8,9,10-tetrahydro-5-MeC, t1/2 = 5.4 vs. 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: 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-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-dihydroxy-syn-9,10-epoxy-7,8,9,10-tetrahydro-5-MeC. Physical interactions with DNA are important in determining the relative extents of binding of these dihydrodiol epoxides to DNA in vitro.

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