Cellular adaptation in metal toxicology and metallothionein

Abstract

The cellular adaptation to toxicity of metals is one of the important factors in the evaluation of health effects of increased exposure to metals. Two major types of cellular effects can be distinguished during divalent metal exposure. Some of the experimental evidences on the role of these processes in the cellular toxicity of metals are reviewed in this article. Both these cellular effects are somewhat specific to certain metals and involve two distinct types of protein binding. One of these processes can be considered as a nuclear process, involving binding of metals to nuclear proteins and also the formation of morphologically distinct inclusion bodies. A number of metals such as lead, bismuth, mercury, copper and aluminium are accumulated intranuclearly and bind with non-histone protein in the nuclei. In addition, morphologically distinct intranuclear inclusion bodies are formed in the kidneys of experimental animals and in humans on continuous exposure to lead or bismuth salts. Another cellular effect of divalent metals is a cytoplasmic process involving a specific metal binding protein, metallothionein. This is a unique metalloprotein containing 2 types of metal cluster and its synthesis is induced by both essential (Zn2+ and Cu2+) and non-essential (Cd2+ and Hg2+) metals. A hypothetical model for metal induced synthesis of metallothioneir is postulated and is partly based on the recent immunohistochemical localization of metallothionein in the nucleus and cytoplasm of both hepatic and renal cells. Although the biological function of the 2 cellular adaptive processes including metal-protein interaction are not yet clearly understood, certain experimental evidence supports the notion that they may provide major sites for intracellular metal binding, thereby reducing the diffusible form of toxic metals within the cell. These 2 processes can be considered as cellular adaptive changes during excessive metal exposure and may have a role in enhancing the tolerance to a number of environmentally ubiquitous metals, particularly divalent metals. © 1983.