Use of genetically altered animal models in understanding the role
of metallothionein in cadmium toxicity*
Curtis D. Klaassen** and Supratim Choudhuri
Department of Pharmacology, Toxicology, and Therapeutics,
University of Kansas Medical Center, Kansas City, KS 66160-7417, USA
Abstract: Acute Cd exposure produces liver injury, whereas chronic
Cd exposure damages the kidney but not the liver. Previous experiments
suggest that the low-molecular-weight, metal-binding protein metallothionein
(MT) in liver protects against liver injury, but is responsible for
the kidney injury observed after chronic Cd exposure. Thus, prior to
the development of MT-transgenic and MT-knockout mice models, MT's role
was always assumed to be a toxicological paradox, hepatoprotection but
nephrotoxicity. The development of MT-transgenic and MT-knockout mice
models has reconfirmed MT's protective role against Cd-induced hepatotoxicity,
but it has challenged MT's suggested role in Cd-induced nephrotoxicity.
In this communication, recent data using these genetically altered mice
models indicate that MT protects against not only the Cd-induced hepatotoxicity,
but also nephrotoxicity, hematotoxicity, immunotoxicity, and bone damage.
*Lectures presented
at the 4th Congress of Toxicology in Developing Countries (4th CTOX-DC),
Antalya, Turkey, 6-10 November 1999
**Corresponding author
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