Metallothionein: analysis in tissues and toxicological significance

The chemical forms of cadmium in tissues can be largely divided into two groups, namely metallothionein (MT)-bound and non-MT-bound. Cadmium accumulates in the body mainly as the former, while the latter, the toxic form of cadmium, can be detected typically in tissues in two cases: (i) before induction of sufficient amounts of MT to sequester cadmium; and (ii) after the accumulation of cadmium in amounts such that it is beyond the capacity of the organ concerned to synthesize enough MT. We identified alcohol dehydrogenase as the major cadmium-binding protein in the liver before induction of MT, though the enzyme activity was not affected by such binding in vivo. The capacity to synthesize MT can be determined from the relative ratio of cadmium to co-existing metals (zinc and copper) in MT, and also by the increase in cadmium in the non-MT-bound form that follows the increase in this ratio. Non-MT-bound cadmium can be detected selectively by a histochemical method using a chelating agent, thiazolylazonaphthol.