蒽环类抗癌抗生素对DNA碱基顺序作用的研究

THE STUDIES ON DNA SEQUENCE PREFERNECE OF ANTHRACYCLINE ANTITUMOR ANTIBIOTICSR

用体外无细胞RNA合成系统对阿克拉霉素B(AcM—B)和阿霉素(ADM)抑制个同DNA模板的依赖DNA的RNA合成作了研究。两药抑制双链NDA模板显著强于单链DNA,作用依次为交序双链DNA(Poly[d(A—T)]和poly[d(G—C)])>同序双链DNA(polydG.polydC和polydA.polydT)》单链DNA(polydA,polydT和polydC)。抑制作用可被增加的DNA模板所逆转。这表明两药主要嵌入DNA双螺旋,特别抑制交序碱基排列的双链DNA.有立体效应。比较双链DNA模板的IC_50证明AcMB和ADM虽然更明显抑制含A—T顺序的DNA,但对A—T和G—C顺序DNA均有显著抑制制。另外AcM—B比ADM抑制DNA顺序的选择性高。

The inhibitory effect of aclacinomycin B (AcM-B) and adriamycin(ADM) on DNA-dependent RNA synthesis directed by different synthetic DNA templates has been studied using non-cell RNA synthesis system in vitro. They inhibit double-stranded DNA templates much stronger than the single-stranded. The order of their inhibition is co-polymers (poly [d (A-T)] and poly[d(G -C)]) > homopolymers (polydA.polydT and polydG.. polydC)>>single-stranded DNA (polydA, polydT, polydC). Our data also showes that the inhibition can be significantly reversed by increasing the amount of DNA templates in the assay. These determined that the two drugs mainly interact with DNA template, not RNA polymerase. They may intercalate into DNA duplex with a sterlc mode because they prefer, cntially block the double-stranded DNA with alternative base sequence. The IC 50 for different copolymers and homopolymers has been determined and indicate that AcM-B and ADM prefer to inhibit DNA containing either A-T sequence or G-C sequence although the inhibition on A-T sequence appears stronger. Our data also provide further evidence that thet effect of Ac M-B on DNA sequence may be more selective than ADM.