The cytopathology of metal overload.

Researchers have been able to demonstrate the cytotoxicity of copper overload in animal models. This has allowed them to not only localize the intracellular distribution of copper but also to study directly the subsequent organelle injury at the ultrastructural level. The lesions seen in copper overload appear to vary from species to species. In humans, marked mitochondrial abnormalities are seen in Wilson's disease while diet overloaded rats show nuclear destruction and various membranous abnormalities. Sequestration of copper within lysosomes appears to protect hepatocytes from its toxicity. However, the mechanism by which the metal is incorporated into lysosomes is not known.