Ferguson L R, Turner P M, Denny W A
Cancer Research Laboratory, University of Auckland Medical School, New Zealand.
Mutat Res. 1990 Oct;232(2):337-43. doi: 10.1016/0027-5107(90)90140-y.
Two series of difunctional DNA-intercalating agents (diacridines and diquinolines) were tested for mutagenic properties in Salmonella typhimurium strain TA1537, and for 'petite' mutagenesis activity in Saccharomyces cerevisiae, and also compared in terms of their structural, lipophilic and DNA-binding properties. Diacridines with only a short chain length were monointercalators, while those with an alkyl linker chain longer than C6 were bisintercalators. Although the bisintercalators especially bound very tightly to DNA, none of these compounds was as effective a frameshift mutagen in TA1537 as the parent chromophore 9-aminoacridine. However, the two (monointercalating) diacridines of shortest chain length were still able to cause frameshifts, and this ability returned (albeit weakly) in the bisintercalators of longest chain length. Although 9-aminoacridine showed no ability for 'petite' mutagenesis, the diacridines of longer chain length were very effective in causing this mitochondrial event. In the quinoline series, both the parent chromophore (4-aminoquinoline) and all the diquinolines were weak monointercalators. None of these compounds showed any ability for frameshift mutagenesis, although some were very weak mitochondrial mutagens. It is concluded that linking two acridines produces compounds whose mutagenic properties might have been predicted from our current knowledge of the parent molecules. However, despite a similar ability to intercalate DNA, the diquinolines show no resemblance to acridines in their mutagenic properties.
测试了两类双功能DNA嵌入剂（二吖啶和二喹啉）在鼠伤寒沙门氏菌TA1537菌株中的诱变特性，以及在酿酒酵母中的“小菌落”诱变活性，并比较了它们的结构、亲脂性和DNA结合特性。链长较短的二吖啶是单嵌入剂，而烷基连接链长于C6的二吖啶是双嵌入剂。尽管双嵌入剂与DNA的结合特别紧密，但在TA1537中，这些化合物作为移码诱变剂，没有一种像母体发色团9-氨基吖啶那样有效。然而，链长最短的两种（单嵌入）二吖啶仍能引起移码，而在链长最长的双嵌入剂中，这种能力（尽管较弱）又恢复了。虽然9-氨基吖啶没有“小菌落”诱变能力，但链长较长的二吖啶在引发这种线粒体事件方面非常有效。在喹啉系列中，母体发色团（4-氨基喹啉）和所有二喹啉都是弱单嵌入剂。这些化合物都没有显示出任何移码诱变能力，尽管有些是非常弱的线粒体诱变剂。得出的结论是，连接两个吖啶产生的化合物，其诱变特性可能可以根据我们目前对母体分子的了解来预测。然而，尽管二喹啉具有类似的嵌入DNA的能力，但其诱变特性与吖啶没有相似之处。
