药物诱变效应与其和DNA园二色谱变化的关系探讨

THE MUTAGENICITY OF DRUGS AND THEIR EFFECT ON DNA CIRCULAR DICHROISM SPECTRA

DNA是药物所致突变效应的分子学基础。园二色谱(CD谱)是研究大分子物质在溶液中构象的1种可靠方法。具有诱变作用的药物如顺铂、碳铂、丝裂霉素C、放线菌素D、高三尖杉酯碱等均影响小牛胸腺DNA的CD谱。而环磷酰胺对DNA的CD谱影响不大,它本身不作用于DNA,需经代谢活化后才具效应。无诱变作用的药物:双酚胺酸、氧化赖氨酸、前者具有强致畸作用,后者能抑制有丝分裂,均不影响CD谱。其它所测试无诱变作用的药物均不影响DNA CD谱。结果表明药物诱变作用及对DNA CD谱的影响具有一定依存关系。

Circular dichroism(CD) is a reliable, scnsitive and convcnicnt method for analysing the effect of drugs on DNA, which inserted into the DNA molccule or formed DNA complex and could change the conformation of DNA, and therefore alter the CD spcctra. Mutagenicity of 19 drugs were tested, while their effects on CD spectra of DNA were measured. These drugs are cisplatin, carboplalin, 10-hydrocamptothccin, actinomycin C homoharringtonine, harringtonine, blcomycin, adriamycine, cyclophosphamidc, catecholamic acid, oxalysine, aniracetam ct al. The calf thymus DNA possesses character ization of CD spectra, which can show a symmctrically positive and negative pcak at 276 and 246 nm rcspectively as well as a positive peak at 217nm, a small negative peak at 206nm. All of mutagcnic drugs effected on CD spectra of DNA, except cyclophosphamidc which need metabolic activation. Effects of various concentration of cisplatin on CD spectra was conducted and rendered a dose-dependant relationship. The change of CD spectra by carboplatin could not be reversed by dialysis for 24 h. Effects of non-mutagcnic drugs were not observed, even though some of them show teratogcnic action (catecholamic acid), inhibition of mitosis in CHL cells (oxalysine). Previous experiment indicated oxalysine might affect RNA, but not DNA. Results suggest that mutagcncsis might be related to the change of CD spectra of DNA, but it need further validating in more chemicals.