CONTEMPORARY-ISSUES IN TOXICOLOGY - ROLE OF METALLOTHIONEIN IN CARCINOGENESIS

Metallothionein (MT) is a low-mo-lecular-weight protein (6800 Da) and one-third of its amino acids are cysteine residues. The 20 cysteines c oordinate 7 metal atoms (zinc, copper, and/or cadmium). This protein i s extremely inducible by metals as well as a number of organic compoun ds. MT is thought to be an important intracellular storage site for zi nc and possibly other essential trace elements. In addition, tolerance to cadmium toxicity is often due to the induction of MT, which seques ters cadmium and lowers its concentration at critical intracellular si tes. Recently it has been proposed that MT might play important roles in several aspects of the carcinogenic process. In this context a symp osium was held recently on this topic at the 1993 Annual Society of To xicology Meeting. At this symposium Dr. Cherian discussed the expressi on of MT in various human tumors and its use as a potential marker of tumor differentiation or cell proliferation. Dr. Imura provided data i llustrating that induction of MT can be used as an adjunct in cancer c hemotherapy, in preventing toxicity caused by gamma-irradiation or cis platin (CDDP) and other chemotherapeutics. Induction of MT has been su ggested to be an important mechanism of resistance of tumor cells to c hemotherapeutic agents, such as CDDP. This is controversial, and vario us views on this topic were presented by Drs. Howell, Late, and Koropa tnick. Dr. Waalkes then discussed the role of MT in the carcinogenic a nd anticarcinogenic effects of metals. (C) 1994 Academic Press, Inc.