Ortega R, Moretto P, Fajac A, Benard J, Llabador Y, Simonoff M
Centre d'Etudes Nucleaires de Bordeaux Gradignan, Cedex, France.
Cell Mol Biol (Noisy-le-grand). 1996 Feb;42(1):77-88.
Platinum and trace metal distributions of a human ovarian adenocarcinoma cell line, IGROV1, and a subline resistant to the antitumor agent cisplatin were compared using nuclear microprobe analysis. The cisplatin-resistant cell line IGROV1-DDP exhibited a cytologically heterogeneous cell population. Two subpopulations were distinguished, small mononuclear cells, morphologically similar to the parental cells IGROV1, and enlarged polynuclear cells. Quantitative mapping of platinum and essential trace metal such as manganese, iron, copper and zinc was performed at the cellular level. Elemental maps were obtained with 2 mu m spatial resolution. Platinum appeared uniformly distributed within the cells, in all cell types. The same was true for copper and zinc. In some cases, iron maps showed preferential localization in the perinuclear region, especially in IGROV1-DDP polynuclear cells. Cisplatin resistance was associated with decreased platinum and iron concentrations and increased levels of copper and zinc. Decreased drug accumulation was encountered in both subpopulations of the resistant cell line. In contrast, high inter-individual variation of copper content was noticed in this cell line suggesting that in vitro cisplatin selection of human ovarian adenocarcinoma resistant cells can bring about the emergence of distinct cellular phenotypes.
利用核微探针分析比较了人卵巢腺癌细胞系IGROV1及其对抗肿瘤药物顺铂耐药的亚系中铂和痕量金属的分布情况。顺铂耐药细胞系IGROV1-DDP表现出细胞学上异质性的细胞群体。区分出两个亚群，即形态上与亲本细胞IGROV1相似的小单核细胞和增大的多核细胞。在细胞水平上对铂和必需痕量金属如锰、铁、铜和锌进行了定量映射。以2微米的空间分辨率获得了元素分布图。在所有细胞类型中，铂在细胞内呈均匀分布。铜和锌也是如此。在某些情况下，铁分布图显示铁在核周区域有优先定位，特别是在IGROV1-DDP多核细胞中。顺铂耐药与铂和铁浓度降低以及铜和锌水平升高有关。在耐药细胞系的两个亚群中均发现药物积累减少。相比之下，在该细胞系中观察到铜含量存在较高的个体间差异，这表明人卵巢腺癌耐药细胞的体外顺铂选择可导致不同细胞表型的出现。
