Metallothioneins and diseases with special reference to cadmium poisoning

Metallothionein (MT) a low molecular weight metal binding protein, is involved in several human diseases. Brain tissue from Alzheimers patients contains lower concentrations of Growth Inhibitory Factor or MT-3. Induction of MT by bismuth increases resistance to renal toxicity of cis-platinum and may be advantageous in can- cer therapy. Cadmium exposure induces MT-syn- thesis in liver, binding Cd and protecting against acute toxicity. Cd-MT is released from liver into plasma, filtered in renal glomerulus and absor- bed in tubules. Lysosomal breakdown of MT releases toxic Cd. This mechanism explains renal tubular damage after long-term exposure to Cd. Impaired tubular regulation of calcium and vita- min D metabolism contributes to the develop- ment of the adverse effects on the skeleton. Quantitative, specific polymerase chain reaction (PCR) studies showed increased expression of mRNA of MT in testicles after Cd exposure, sup- porting the notion that MT increases cellular resistance to metals and protects from Cd toxi- city. This idea was advanced by one of the pre- sent authors thirty years ago.