CLONAL VARIATION OF CADMIUM RESPONSE IN HUMAN-TUMOR CELL-LINES
CLONAL VARIATION OF CADMIUM RESPONSE IN HUMAN-TUMOR CELL-LINES
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DOI：
10.1152/ajpcell.1986.250.2.c256
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发表时间：
1986-02-01
影响因子：
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通讯作者：
BARHAM, SS
中科院分区：
文献类型：
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作者：
ENGER, MD;TESMER, JG;BARHAM, SS
对人肿瘤衍生细胞系A101 D、A204和A549的亚群进行Cd 2+细胞毒性反应筛选。发现六个A549中的三个、七个A101 D中的两个和七个A204亚群中的四个与亲本系显著不同。流式细胞术显示A101 D（T3）的变体亚群由具有两个不同DNA直方图的细胞组成。一个直方图，1型，类似于正常人成纤维细胞的直方图。另一种是2型，代表DNA多三分之一的细胞。早期传代T3克隆群体主要由1型细胞组成。随着传代，1型细胞相对于2型细胞减少，因此到第47代，培养物主要为2型。相应地，随着培养时间的延长，A101 D T3亚群对Cd ~（2+）变得更加敏感。发现仅具有1型DNA直方图的亚克隆相对于具有2型直方图的亚克隆是Cd 2+抗性的，并且用2 μ M Cd 2+处理具有大致等量的1型和2型细胞的A101 D T3培养物导致选择1型细胞。A101 D T3 1型细胞表现出的增强的Cd 2+抗性表型与Cd 2+摄取减少相关，并且不归因于增强的金属硫蛋白合成。
Subpopulations of human tumor-derived cell lines A101D, A204, and A549 were screened for Cd2+ cytotoxic response. Three of six A549, two of seven A101D, and four of seven A204 subpopulations were found to differ significantly from the parental line. A variant subpopulation of A101D (T3) was shown by flow cytometry to be comprised of cells having two distinct DNA histograms. One histogram, type 1, resembles that of normal human fibroblasts. The other, type 2, represents cells with one-third more DNA. Early passage T3 clonal populations were comprised primarily of type 1 cells. With passage, type 1 cells decreased relative to type 2 so that by passage 47 the culture was predominantly type 2. Correspondingly, the A101D T3 subpopulation became more Cd2+ sensitive with time in culture. Subclones having only type 1 DNA histograms were found to be Cd2+ resistant relative to subclones with type 2 histograms, and treatment of A101D T3 cultures having approximately equal amounts of type 1 and 2 cells with 2 .mu.M Cd2+ resulted in the selection of type 1 cells. The enhanced Cd2+ resistance phenotype shown by A101D T3 type 1 cells correlated with reduced Cd2+ uptake and is not attributable to enhanced metallothionein synthesis.