Murray V, Whittaker J, McFadyen W D
School of Biochemistry and Molecular Genetics, University of New South Wales, Sydney, Australia.
Chem Biol Interact. 1998 Mar 12;110(1-2):27-37. doi: 10.1016/s0009-2797(97)00110-5.
The sequence specificity of ten cisplatin analogues was examined in intact human cells. Six of these compounds have anti-tumour activity. The sequence selectivity was investigated using a Taq DNA polymerase/linear amplification assay on damaged DNA extracted from treated cells. Cisplatin and tetraplatin(IV) produced strong damage and DACH RR(II) and cis-[Pt(II)Cl,2(iPrNH2)2] weak DNA damage in intact HeLa cells. The sequence selectivity of tetraplatin(IV) in intact human cells was very similar to that of cisplatin and favored runs of consecutive purines, especially consecutive guanines. The compounds transplatin, carboplatin, cis-[PtCl(NH3)2(C8H17.NH2)], cis-[PtCl2(iPentNH2)2], cis-[PtCl2(C6H11NH2)2, DACH SS(II) and CHIP(IV) did not significantly damage DNA in cells. It was concluded that the interactions of these cisplatin analogues with DNA in human cells were strongly influenced by their ability to damage purified DNA.
在完整的人类细胞中检测了十种顺铂类似物的序列特异性。这些化合物中有六种具有抗肿瘤活性。使用Taq DNA聚合酶/线性扩增分析法对从处理过的细胞中提取的受损DNA进行了序列选择性研究。在完整的HeLa细胞中，顺铂和四价铂（IV）造成强烈损伤，而二氨基环己烷RR（II）和顺式-[Pt（II）Cl₂（异丙胺）₂]造成较弱的DNA损伤。四价铂（IV）在完整人类细胞中的序列选择性与顺铂非常相似，且倾向于连续嘌呤序列，尤其是连续鸟嘌呤。反式铂、卡铂、顺式-[PtCl（NH₃）₂（C₈H₁₇·NH₂）]、顺式-[PtCl₂（异戊胺）₂]、顺式-[PtCl₂（C₆H₁₁NH₂）₂]、二氨基环己烷SS（II）和CHIP（IV）在细胞中不会显著损伤DNA。得出的结论是，这些顺铂类似物与人类细胞中DNA的相互作用受到其损伤纯化DNA能力的强烈影响。
