TOXICOKINETICS AND BIOCHEMISTRY OF CADMIUM WITH SPECIAL EMPHASIS ON THE ROLE OF METALLOTHIONEIN

Cadmium is a toxic metal with extremely long biological half-time of 1 5-20 years in humans. It has for decades been known that cadmium expos ure can cause a variety of adverse health effects, among which kidney dysfunction, lung diseases, disturbed calcium metabolism and bone effe cts are most prominent. Following long term exposure the kidney is the critical organ. Cadmium and its compounds give rise to lung cancer af ter inhalation and have been classified as human carcinogens. Metallot hionein (MT) is a low-molecular -weight protein, 6500Da with high cyst eine content and high metal affinity, which plays a major role in the kinetics and metabolism of cadmium. The balance between CdMT and non-b ound Cd in renal tissue has been shown to be of crucial importance for expression of toxicity. The most well studied metallothioneins are me tallothioneins I and II with their isoforms which are expressed in alm ost all mammalian tissues. Metallothionein III is expressed in brain a nd is rich in zinc. Since the blood-brain barrier keeps Cd outside the CNS, reported neurotoxic effects of Cd during development are likely to be secondary to an interference of Cd with Zn-metabolism and not a direct effect of Cd on brain cells. It is therefore of importance to i nvestigate whether neurotoxicity induced by cadmium is related to mech anisms involving MT III in brain. (C) 1998 Inter Press, Inc.