ABSTRACT Metallothioneins (MTs) have been defined as intracellular, low molecular weight proteins of high cysteine and heavy metal contents. They have been proposed as chelators and detoxifiers to harmful heavy metals and excessive essential metals, scavengers to oxygen free radicals, regulators in the cell proliferation process and as protective agents against stress. Four main isoforms MT-1, MT-2, MT-3 and MT-4 have been identified in mammalian cells and their synthesis is induced by both essential (Zn+2 and Cu+2) and non-essential (Cd+2 and Hg+2) metals. The inducibility of the MTs by heavy metals and the subsequent metal accumulation in the cell have been used as biomarkers in the field of environmental toxicology. Furthermore, the role of MT-1 and MT-2 isoforms in zinc homeostasis and apoptosis is of great importance. This article reviews the global toxicological significance of metallothioneins and their relationship to other antioxidant defense systems.
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