THE CELLULAR TOXICITY OF ALUMINUM

Aluminium is a serious environmental toxicant and is inimical to biota. Omnipresent, it is linked with a number of disorders in man including Alzheimer's disease, Parkinson's dementia and osteomalacia. Evidence supporting aluminium as an aetiological agent in such disorders is not conclusive and suffers principally from a lack of consensus with respect to aluminium's toxic mode of action. Obligatory to the elucidation of toxic mechanisms is an understanding of the biological availability of aluminium. This describes the fate of and response to aluminium in any biological system and is thus an important influence of the toxicity of aluminium. A general theme in much aluminium toxicity is an accelerated cell death. Herein mechanisms are described to account for cell death from both acute and chronic aluminium challenges. Aluminium associations with both extracellular surfaces and intracellular ligands are implicated. The cellular response to aluminium is found to be biphasic having both stimulatory and inhibitory components. In either case the disruption of second messenger systems is observed and GTPase cycles are potential target sites. Specific ligands for aluminium at these sites are unknown though are likely to be proteins upon which oxygen-based functional groups are orientated to give exceptionally strong binding with the free aluminium ion. © 1992 Academic Press Limited All rights reserved.