Cherian M G, Howell S B, Imura N, Klaassen C D, Koropatnick J, Lazo J S, Waalkes M P
Department of Pathology, University of Western Ontario, London, Canada.
Toxicol Appl Pharmacol. 1994 May;126(1):1-5. doi: 10.1006/taap.1994.1083.
Metallothionein (MT) is a low-molecular-weight protein (6800 Da) and one-third of its amino acids are cysteine residues. The 20 cysteines coordinate 7 metal atoms (zinc, copper, and/or cadmium). This protein is extremely inducible by metals as well as a number of organic compounds. MT is though to be an important intracellular storage site for zinc and possibly other essential trace elements. In addition, tolerance to cadmium toxicity is often due to the induction of MT, which sequesters cadmium and lowers its concentration at critical intracellular sites. Recently it has been proposed that MT might play important roles in several aspects of the carcinogenic process. In this context a symposium was held recently on this topic at the 1993 Annual Society of Toxicology Meeting. At this symposium Dr. Cherian discussed the expression of MT in various human tumors and its use as a potential marker of tumor differentiation or cell proliferation. Dr. Imura provided data illustrating that induction of MT can be used as an adjunct in cancer chemotherapy, in preventing toxicity caused by gamma-irradiation or cisplatin (CDDP) and other chemotherapeutics. Induction of MT has been suggested to be an important mechanism of resistance of tumor cells to chemotherapeutic agents, such as CDDP. This is controversial, and various views on this topic were presented by Drs. Howell, Lazo, and Koropatnick. Dr. Waalkes then discussed the role of MT in the carcinogenic and anticarcinogenic effects of metals.
金属硫蛋白（MT）是一种低分子量蛋白质（6800道尔顿），其三分之一的氨基酸为半胱氨酸残基。20个半胱氨酸与7个金属原子（锌、铜和/或镉）配位。这种蛋白质极易被金属以及多种有机化合物诱导产生。MT被认为是锌以及可能其他必需微量元素的重要细胞内储存位点。此外，对镉毒性的耐受性通常归因于MT的诱导，MT可螯合镉并降低其在关键细胞内位点的浓度。最近有人提出MT可能在致癌过程的多个方面发挥重要作用。在此背景下，最近在1993年毒理学会年会上就该主题举行了一次研讨会。在这次研讨会上，切里安博士讨论了MT在各种人类肿瘤中的表达及其作为肿瘤分化或细胞增殖潜在标志物的用途。井村博士提供的数据表明，MT的诱导可作为癌症化疗的辅助手段，用于预防γ射线照射或顺铂（CDDP）及其他化疗药物引起的毒性。MT的诱导被认为是肿瘤细胞对化疗药物（如CDDP）产生耐药性的重要机制。这一观点存在争议，豪厄尔博士、拉佐博士和科罗帕特尼克博士就此主题提出了各种观点。瓦尔克斯博士随后讨论了MT在金属致癌和抗癌作用中的作用。
