Lohrer H, Robson T
Cancer Research Unit, University of Newcastle upon Tyne, Medical School, UK.
Carcinogenesis. 1989 Dec;10(12):2279-84. doi: 10.1093/carcin/10.12.2279.
Metallothionein protein protects cells from the toxic effects of heavy metal ions. To establish its protective function against ionizing radiation and alkylating agents, a model system was created by transfecting two CHO cell lines (wild-type, K1-2 and X-ray sensitive, xrs-2 subclone Bc11) with the human metallothionein II-A (hMTII-A) gene integrated in a bovine papilloma derived autonomously replicating vector. The isolated transfectants are cadmium-resistant (Cdr), due to the overexpression of the hMTII-A gene. Their steady-state level of hMTII-A mRNA can be increased up to 40-fold after Cd treatment and 20-fold after induction with ionizing radiation. The transfected cell lines proved to be as sensitive as the recipient cell lines to ionizing radiation and bleomycin but the transfectants were significantly more resistant to N-methyl-N'-nitro-N'-nitrosoguanidine (MNNG) and mitomycin C (MMC). These results lead to the conclusion that the MT protein does provide a defence mechanism to protect cells from monofunctional alkylating and cross-linking agents but not from free radicals.
金属硫蛋白可保护细胞免受重金属离子的毒性作用。为确定其对电离辐射和烷化剂的保护功能，构建了一个模型系统，将整合于牛乳头瘤病毒衍生的自主复制载体中的人金属硫蛋白II - A（hMTII - A）基因转染至两种中国仓鼠卵巢细胞系（野生型K1 - 2和对X射线敏感的xrs - 2亚克隆Bc11）。由于hMTII - A基因的过表达，分离得到的转染子具有镉抗性（Cdr）。经镉处理后，其hMTII - A mRNA的稳态水平可增加至40倍，经电离辐射诱导后可增加至20倍。结果表明，转染细胞系对电离辐射和博来霉素的敏感性与受体细胞系相同，但转染子对N - 甲基 - N' - 硝基 - N' - 亚硝基胍（MNNG）和丝裂霉素C（MMC）的抗性显著更高。这些结果得出结论，金属硫蛋白确实提供了一种防御机制，可保护细胞免受单功能烷化剂和交联剂的损伤，但不能保护细胞免受自由基的损伤。
