Chubatsu L S, Gennari M, Meneghini R
Department of Biochemistry, University of São Paulo, Brazil.
Chem Biol Interact. 1992 Mar;82(1):99-110. doi: 10.1016/0009-2797(92)90017-f.
By manipulation of Cd and Zn concentrations in the medium, several phenotypes, differing in the contents of glutathione (GSH) and metallothionein (Mt), were derived from a parental clone of V79 Chinese hamster fibroblast. In some of these phenotypes, resistance to Cd and cross-resistance to oxidative stress was developed. The highest levels of GSH and Mt were found in cells which were rendered resistant to Cd by stepwise increases of Cd and Zn in the cell medium for over 50 passages. Upon removal of Cd/Zn from the medium of these cells or addition of Cd/Zn to the parental cell medium, changes of cellular GSH and Mt levels occurred to different extents. At the same time, changes in the resistance to Cd and H2O2 were observed. Good linear correlations were observed for Mt levels x resistance to Cd and for GSH levels x resistance to H2O2. Poor linear correlations were found for Mt levels x resistance to H2O2 or for GSH levels x resistance to Cd. Moreover, addition of Zn to the medium produced an increase in Mt content without affecting the GSH content. In this case no cross-resistance to oxidative stress was developed. Therefore, Mt which has been shown to be an excellent antioxidant in in vitro experiments, does not seem to play any major role against oxidative stress in Zn and Cd challenged cells. Most of the cross-resistance to oxidative stress in Cd challenged cells seems to be accounted for by the parallel increase in GSH.
通过控制培养基中镉（Cd）和锌（Zn）的浓度，从V79中国仓鼠成纤维细胞的亲代克隆中获得了几种谷胱甘肽（GSH）和金属硫蛋白（Mt）含量不同的表型。在其中一些表型中，细胞产生了对Cd的抗性以及对氧化应激的交叉抗性。在通过在细胞培养基中逐步增加Cd和Zn超过50代而获得的对Cd具有抗性的细胞中，发现了最高水平的GSH和Mt。当从这些细胞的培养基中去除Cd/Zn或向亲代细胞培养基中添加Cd/Zn时，细胞内GSH和Mt水平发生了不同程度的变化。与此同时，观察到对Cd和过氧化氢（H2O2）抗性的变化。Mt水平与对Cd的抗性以及GSH水平与对H2O2的抗性之间呈现出良好的线性相关性。而Mt水平与对H2O2的抗性或GSH水平与对Cd的抗性之间的线性相关性较差。此外，向培养基中添加Zn会使Mt含量增加，而不影响GSH含量。在这种情况下，不会产生对氧化应激的交叉抗性。因此，尽管Mt在体外实验中已被证明是一种出色的抗氧化剂，但在受到Zn和Cd挑战的细胞中，它似乎并未在抵抗氧化应激方面发挥任何主要作用。Cd挑战细胞中对氧化应激的大部分交叉抗性似乎是由GSH的平行增加所导致的。
