DNA alkylation and unwinding induced by benzo[a]pyrene diol epoxide: modulation by ionic strength and superhelicity.
AUTOR(ES)
Gamper, H B
RESUMO
Superhelical and partially relaxed DNAs of simian virus 40 were allowed to react in vitro with (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaP diol epoxide). The modified DNA contained N2 guanine and N6 adenine hydrocarbon adducts in the ratio 86:14. Superhelical simian virus 40 DNA was approximately 6% more susceptible to modification than was partially relaxed viral DNA. Counterions inhibited DNA alkylation by up to 90%, Mg2+ being 50-fold more effective than Na+. The sensitivity of covalent binding to helix stability is consistent with a reaction complex in which BaP diol epoxide is intercalated. The superhelical density of the modified DNA substrates was determined electrophoretically relative to partially relaxed standards, and an unwinding angle for the hydrocarbon adducts was calculated. The angle was dependent upon the superhelicity of the DNA molecule and ranged from 330 degrees to 30 degrees. These data indicate that the modified base pairs are disrupted and, in the presence of torsional strain, act as centers for the further denaturation of up to eight adjacent base pairs. In the absence of such strain the alkylation sites have an ordered structure, with the attached hydrocarbon probably oriented in the minor or major groove of the helix.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=348638Documentos Relacionados
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