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Differences in the Binding of Stereoisomeric Benzo(a)pyrene-7,8-diol-9,10-epoxides to Histones in Rat Liver Nuclei¹

The University of Texas System Cancer Center, Science Park-Research Division, Smithville, Texas 78957

We have compared the covalent binding of two stereoisomeric benzo(a)pyrene-7,8-diol-9,10-epoxides to histones. From rat liver nuclei exposed to carcinogenic [³H]-(±)-7r,8t-dihydroxy-9t,10t-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene ([³H]BPDE-I) or noncarcinogenic [³H]-(±)-7r,8t-dihydroxy-9c,10c-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene ([³H]BPDE-II), H1 and core histone fractions were prepared by differential acid extraction. The specific activity (dpm/mg protein) of the core histone fraction for [³H]BPDE-I was much higher than that of [³H]BPDE-II. Alternatively in the H1 histone fraction, the binding level of [³H]BPDE-I was lower than that of [³H]BPDE-II. By reverse-phase high performance liquid chromatography, the analyses of BPDE isomers binding to histones showed that histones H2A and H1 were heavily labeled by [³H]BPDE-I and -II, respectively. In particular, the ratio of specific activities for BPDE-I to II in peak C3, which mainly contains H2A·2 variant, was higher than those of other histone H2A variants and other core histones. These results indicate that the BPDE isomers have differential binding affinities to histones. The covalent binding of BPDE-I to histone H2A (especially H2A·2 variant) may be important in the potential carcinogenic effects in nuclei.

¹ Research supported by Grant CA 35581-01 from the National Cancer Institute and a gift from the University Cancer Foundation.

² To whom requests for reprints should be addressed.

Received 12/26/84. Revised 7/12/85. Accepted 7/24/85.