Gick G G, McCarty K S
Toxicology. 1983 Mar-Apr;26(3-4):275-83. doi: 10.1016/0300-483x(83)90088-4.
A clonal cell line, R40F, was selected from a heterogenous population of Cd2+ and Zn2+-resistant CHO-K1 cells. These R40F cells demonstrated resistance to 120- and 4-fold higher concentrations of Cd2+ and Zn2+, respectively, than did wild type CHO-K1 cells. When cultured in the presence of low concentrations of Cd2+ (0.5-1.0 microM), the accumulation of intracellular Cd2+ in R40F cells appears to be significantly less than in wild type cells. Since R40F cells maintained in medium containing high concentrations of Cd2+ (200 microM) retain levels of Cd2+ equivalent to the intracellular concentration observed in wild type cells exhibiting cytotoxicity, it is assumed that reduced Cd2+ transport alone is unlikely to account for the resistance to Cd2+ toxicity. Exposure of R40F cells to non-toxic (2 microM or 100 microM) or toxic (200 microM) Zn2+ levels resulted in an accumulation of Zn2+ equal to, or greater than, that observed in the wild type cell. When compared to the basal level in uninduced wild type cells, metallothionein levels were elevated 14- and 23-fold, respectively, in R40F cells cultured in the presence of 0.5 microM Cd2+ and 100 microM Zn2+. These results are consistent with the hypothesis that R40F cells express Cd2+ and Zn2+ resistance as a consequence of a reduction in unbound intracellular Cd2+ levels and an elevation of metallothionein synthesis.
从耐镉离子（Cd2+）和锌离子（Zn2+）的CHO-K1细胞异质群体中筛选出一种克隆细胞系R40F。这些R40F细胞对Cd2+和Zn2+的耐受浓度分别比野生型CHO-K1细胞高120倍和4倍。当在低浓度Cd2+（0.5 - 1.0 microM）存在的情况下培养时，R40F细胞内Cd2+的积累似乎明显少于野生型细胞。由于在含有高浓度Cd2+（200 microM）的培养基中培养的R40F细胞所保留的Cd2+水平与表现出细胞毒性的野生型细胞中观察到的细胞内浓度相当，因此推测仅Cd2+转运减少不太可能解释对Cd2+毒性的抗性。将R40F细胞暴露于无毒（2 microM或100 microM）或有毒（200 microM）的Zn2+水平下，导致Zn2+的积累量等于或大于野生型细胞中观察到的积累量。与未诱导的野生型细胞的基础水平相比，在含有0.5 microM Cd2+和100 microM Zn2+的培养基中培养的R40F细胞中金属硫蛋白水平分别升高了14倍和23倍。这些结果与以下假设一致，即R40F细胞由于细胞内未结合的Cd2+水平降低和金属硫蛋白合成增加而表现出对Cd2+和Zn2+的抗性。
