Induction and repair of DNA cross-links in chinese hamster ovary cells treated with various platinum coordination compounds in relation to platinum binding to DNA, cytotoxicity, mutagenicity, and antitumor activity.
Induction and repair of DNA cross-links in chinese hamster ovary cells treated with various platinum coordination compounds in relation to platinum binding to DNA, cytotoxicity, mutagenicity, and antitumor activity.
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用各种铂配位化合物处理的中国仓鼠卵巢细胞中 DNA 交联的诱导和修复与铂与 DNA 的结合、细胞毒性、致突变性和抗肿瘤活性有关。
作者：
A. C. Plooy;M. Dijk;P. Lohman
研究了四种二胺氯铂化合物（II和IV）对中国仓鼠卵巢细胞的影响。已知两种顺式化合物[顺式二胺二氯铂（II）和顺式二胺四氯铂（IV）]具有抗肿瘤活性，而两种反式立体异构体[反式二胺二氯铂（II）和反式二胺四氯铂（IV）]则无活性。在将等量铂与细胞DNA结合处理后，比较顺式和反式铂化合物的作用，发现以下差异：(a)顺式铂加合物具有更高的细胞毒性；(b)只有顺式铂- dna复合物具有强诱变性（在次黄嘌呤-鸟嘌呤磷酸核糖基转移酶位点发生正向突变）；(c)顺铂加合物诱导更多姊妹染色单体交换；(d)顺式化合物最初诱导较少的dna -蛋白质交联（因子5至8），但这些顺式-铂交联更持久；(e)对于两种顺式复合物，DNA链间交联的数量在处理后6 ~ 12小时达到最大值，并且交联修复缓慢。一种反式化合物[反式二胺四氯铂（IV）]在这类病变形成和消失的总体动力学方面与顺式复合物相似，但修复速度更快。对于另一种反式化合物[反式二胺二氯铂（II）]，在细胞处理后直接检测到最高数量的交联，并且它们被迅速消除。铂-DNA损伤的数量本身和DNA链间交联的初始数量都与化合物的（基因）毒性作用无关。然而，由于顺铂诱导的链间和dna -蛋白交联的缓慢修复导致这些加合物的一定持久性，未修复的病变可能是细胞毒性、致突变性和抗肿瘤活性的原因。这表明修复系统对某些顺式或反式铂dna加合物具有区别性。姐妹染色单体交换诱导似乎与持续的DNA链间交联有关。
Several effects of four diamminechloroplatinum compounds (II and IV) in Chinese hamster ovary cells were studied. The two cis-compounds [cis-diamminedichloroplatinum(II) and cis-diamminetetrachloroplatinum(IV)] are known to possess antitumor activity, whereas the two trans-stereoisomers [trans-diamminedichloroplatinum(II) and trans-diamminetetrachloroplatinum(IV)] are inactive. When the effects of the cis-and trans-platinum compounds were compared after treatments that resulted in the binding of equal amounts of platinum to the DNA of the cells, the following differences were found: (a) the cis-platinum adducts gave a much higher cytotoxicity; (b) only the cis-platinum-DNA complexes were strongly mutagenic (forward mutations at the hypoxanthine-guanine phosphoribosyltransferase locus); (c) the cis-platinum adducts induced more sister chromatid exchanges; (d) the cis compounds initially induced fewer DNA-protein cross-links (Factors 5 to 8), but these cis-platinum cross-links were much more persistent; (e) for both cis complexes, the amount of DNA interstrand cross-links passed through a maximum between 6 and 12 hr after treatment, and the cross-links were repaired slowly. One trans-compound [trans-diamminetetrachloroplatinum(IV)] resembled the cis complexes with respect to the overall kinetics of formation and disappearance of this type of lesion, but the repair went faster. For the other trans compound [trans-diamminedichloroplatinum(II)], the highest number of cross-links was detected directly after the treatment of the cells, and they were rapidly eliminated. Neither the number of platinum-DNA lesions as such nor the initial amount of DNA interstrand cross-links could be related to the (geno)toxic effects of the compounds. However, as the slow repair of the cis-platinum-induced interstrand and DNA-protein cross-links leads to a certain persistency of these adducts, the unrepaired lesions might be responsible for cytotoxicity, mutagenicity, and antitumor activity. This indicates discriminating properties of the repair systems for certain cis-or trans-platinum-DNA adducts. The sister chromatid exchange induction seems to be related to the persistent DNA interstrand cross-links.
DNA 交联对顺式二氯二氨铂 (II) 诱导的小鼠白血病 L1210 细胞敏感和耐药系细胞毒性的意义。
影响因子：
5.1
作者：
Strandberg,MC;Bresnick,E;Eastman,A
通讯作者：
Eastman,A
使用核酸外切酶 III 确定 DNA 确定序列中稳定损伤的位点：环丁烷嘧啶二聚体以及顺式和反式二氯二氨铂 II 示例。
影响因子：
14.9
作者：
Royer-Pokora,B;Gordon,LK;Haseltine,WA
通讯作者：
Haseltine,WA