Plooy A C, Lohman P H
Toxicology. 1980;17(2):169-76. doi: 10.1016/0300-483x(80)90090-6.
Ten platinum (Pt) coordination complexes with different ligands, comprising both Pt(II) and Pt(IV) complexes of which the cis-compounds all possessed at least some anti-tumour activity and the trans-compounds were inactive, were tested as to their effect on cell survival and the induction and repair of DNA damage in cultured Chinese hamster cells (CHO). The tests used were the determination of cytotoxicity, inhibition of the semi-conservative DNA replication, induction of damage in DNA and mutagenicity. The Pt-compounds could be divided in 3 groups on the basis of their cytotoxicity. The compounds with high cytotoxicity were also active anti-tumour drugs, but a clear correlation between cytotoxicity and anti-tumour activity was not observed. All compounds inhibited semi-conservative DNA synthesis and induced DNA repair replication. No induction of DNA single strand breaks and DNA cross-links was detected. However, the occurrence of alkali labile sites in the DNA of treated CHO cells demonstrated the induction of unidentified DNA base damages. The 4 compounds tested so far, 2 cis- and 2 trans-Pt complexes, induced mutations in CHO cells, leading to resistance to 6-thioguanine; the cis-compounds were more mutagenic than the trans-compounds.
测试了十种带有不同配体的铂（Pt）配位化合物，其中包括Pt（II）和Pt（IV）配合物，所有顺式化合物均具有至少一定的抗肿瘤活性，而反式化合物则无活性，研究了它们对培养的中国仓鼠细胞（CHO）的细胞存活以及DNA损伤的诱导和修复的影响。所采用的测试包括细胞毒性测定、对半保留DNA复制的抑制、DNA损伤的诱导和致突变性。根据细胞毒性，Pt化合物可分为3组。具有高细胞毒性的化合物也是活性抗肿瘤药物，但未观察到细胞毒性与抗肿瘤活性之间存在明显相关性。所有化合物均抑制半保留DNA合成并诱导DNA修复复制。未检测到DNA单链断裂和DNA交联的诱导。然而，处理过的CHO细胞DNA中碱不稳定位点的出现证明了未鉴定的DNA碱基损伤的诱导。迄今为止测试的4种化合物，2种顺式和2种反式Pt配合物，在CHO细胞中诱导突变，导致对6-硫鸟嘌呤产生抗性；顺式化合物比反式化合物更具致突变性。
