Mattern I E, Cocchiarella L, van Kralingen C G, Lohman P H
Mutat Res. 1982 Aug;95(2-3):79-93. doi: 10.1016/0027-5107(82)90248-2.
11 platinum compounds with nitrogen donor ligands, previously tested for anti-tumour activity, were studied for induction of prophage lambda and for mutagenicity in the Ames assay, with various strains of Salmonella. The compounds included cis and trans isomers of Pt(II) and Pt(IV) complexes and were tested with and without metabolic activation. All the cis compounds elicited prophage induction, whereas the trans compounds were inactive. Mutagenicity was found only in strains containing the R factor, indicating that SOS-type repair processes are required for the conversion of initial DNA lesions into mutations. Mutation induction was also influenced by the excision-repair process. The 2 trans compounds were not, or only slightly, mutagenic; all other compounds were mutagenic in at least one strain, exhibiting a 2-20-fold increase over the spontaneous background level. Addition of liver homogenate had no significant effect on the number of mutants. One compound induced exclusively frameshift mutations. The other mutagenic compounds induced frameshift mutations as well as base-pair substitutions. 7 compounds were more mutagenic for the repair-proficient than for the repair-deficient strains; only one showed the opposite effect. This suggests that for mutagenicity testing of platinum compounds, repair-proficient strains are more sensitive indicators. The differences in response of the various strains are more sensitive indicators. The differences in response of the various strains toward the compounds suggest the formation of different DNA lesions and/or a selective action of repair processes on these lesions. In general, a good qualitative correlation was observed between prophage-inducing capacity, mutagenicity in bacterial and mammalian cells and anti-tumour activity.
对11种先前已测试过抗肿瘤活性的含氮供体配体的铂化合物进行了研究，检测其对λ噬菌体的诱导作用以及在艾姆斯试验中对各种沙门氏菌菌株的致突变性。这些化合物包括Pt(II)和Pt(IV)配合物的顺式和反式异构体，并在有和没有代谢激活的情况下进行了测试。所有顺式化合物都能诱导噬菌体，而反式化合物则无活性。仅在含有R因子的菌株中发现了致突变性，这表明初始DNA损伤转化为突变需要SOS型修复过程。突变诱导也受切除修复过程的影响。2种反式化合物无致突变性或仅有轻微致突变性；所有其他化合物在至少一种菌株中具有致突变性，比自发背景水平增加了2至20倍。添加肝匀浆对突变体数量没有显著影响。一种化合物仅诱导移码突变。其他致突变化合物既诱导移码突变也诱导碱基对置换。7种化合物对修复 proficient菌株的致突变性比对修复 deficient菌株更强；只有一种表现出相反的效果。这表明对于铂化合物的致突变性测试，修复 proficient菌株是更敏感的指标。各种菌株反应的差异是更敏感的指标。各种菌株对这些化合物反应的差异表明形成了不同的DNA损伤和/或修复过程对这些损伤的选择性作用。一般来说，在噬菌体诱导能力、细菌和哺乳动物细胞中的致突变性以及抗肿瘤活性之间观察到了良好的定性相关性。
