J. Biol. Chem., Vol. 256, Issue 3, 1263-1268, Feb, 1981
Differential pulse polarographic determination of murine metallothionein induction kinetics
RW Olafson
Quantitative determination of tissue levels of metallothionein was
performed using differential pulse polarographic analysis. Cadmium
induction of mouse hepatic metallothionein was observed to be linear with
respect to dose until a sharp saturation maximum was reached. This
metal-stimulated synthesis was completely inhibited by actinomycin D. It
was found that a 2- and 7-fold molar excess of copper and zinc,
respectively, was necessary to induce hepatic metallothionein synthesis
equivalent to a single dose of cadmium. Although liver was the most dynamic
tissue in terms of synthetic production, the intestine had the highest
basal level. However, induction in the latter tissue was greatly decreased
relative to liver or kidney, with no measurable synthesis after a single
metal dose. Induction kinetics was similar for all inducing metals with the
exception of cadmium-induced hepatic protein, which remained unchanged for
2 weeks and decayed with an apparent t 1/2 of 32 days. Furthermore, with
the exception of intravenous zinc dosing, which elicited no hepatic
biosynthesis, initial induction kinetics was invariant with administration
route. It was observed that chronic subcutaneous administration of
sufficient cadmium to saturate hepatic metallothionein synthesis resulted
in a coincident onset of toxic symptoms.
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