Morier-Teissier E, Bernier J L, Coulaud D, Hénichart J P, Delain E
Unité INSERM No 16, CHR Place de Verdun, Lille, France.
J Biomol Struct Dyn. 1992 Feb;9(4):653-66. doi: 10.1080/07391102.1992.10507946.
Electron microscopy was used to analyse the precipitation of DNA observed when mixed with two tripeptide derivatives of mitoxantrone, with or without a 5,8-dihydroxy group (DHQ-GHK and Q-GHK, respectively) on the anthraquinonic ring. This precipitation was compared to that obtained with the basic drugs, mitoxantrone (DHAQ) and ametantrone (AQ). The effects of these compounds on the supercoiling of form I and the lengthening of form II of pBR322 DNA molecules, respectively, were evaluated. A strong lengthening of the DNA molecules was observed for ametantrone (max: 57%), but only 32% for Q-GHK, both at r (drug/base pari) = 250. With the dihydroxy derivative DHQ-GHK, it was not possible to show more than a 10% increase in length because DNA molecules were not measurable at r greater than 100. Only Q-GHK relaxed supercoiled molecules at the low r values of 10. Complex phenomena of condensation-precipitation were observed with these two tripeptide derivatives. In addition to a strong lengthening of form II DNA molecules, AQ induced specifically the formation of toruses, and DHAQ that of large organized DNA condensation. The variety of the aggregations is described and discussed with regard to the antitumor properties of these derivatives, and the literature concerning the various descriptions of DNA aggregation.
利用电子显微镜分析了米托蒽醌的两种三肽衍生物（分别在蒽醌环上带有或不带有5,8 - 二羟基基团，即DHQ - GHK和Q - GHK）与DNA混合时观察到的DNA沉淀情况。将这种沉淀与碱性药物米托蒽醌（DHAQ）和氨甲蒽醌（AQ）所产生的沉淀进行了比较。分别评估了这些化合物对pBR322 DNA分子的I型超螺旋和II型延长的影响。在r（药物/碱基对）= 250时，观察到氨甲蒽醌使DNA分子有强烈的延长（最大值：57%），但Q - GHK仅为32%。对于二羟基衍生物DHQ - GHK，由于在r大于100时DNA分子无法测量，所以无法显示出长度增加超过10%。只有Q - GHK在r值低至10时能使超螺旋分子松弛。观察到这两种三肽衍生物出现了复杂的凝聚 - 沉淀现象。除了使II型DNA分子强烈延长外，AQ还特异性地诱导形成环面，而DHAQ诱导形成大的有组织的DNA凝聚物。针对这些衍生物的抗肿瘤特性以及有关DNA聚集的各种描述的文献，对聚集的多样性进行了描述和讨论。
