The Amount of Metals Sufficient to induce the Production of Metallothionein in Rat Liver

Abstract

Rats were injected intravenously with graded amounts of four metals ; Cd, Hg and Zn which induced metallothionein (MT) and Se which could not. They all contained their radioisotopes. The metal contents in the liver, its cytosol and each fraction of the cytosol obtained by Sephadex G-75 column chromatography were estimated by measuring their specific radioactivities. Hg incorporated into the liver accumulated in the cytosol especially in its MT fraction. Approximately 70% of Cd incorporated into the liver distributed to the cytosol and substantially Cd (more than 80%) in the cytosol distributed in its MT fraction. The 6-9% of Zn incorporated into the liver and 50-64% of Zn in the liver was found in its cytosol. About 2% of Se incorporated into the liver distributed to the MT fraction. On the other hand, from the fact that the high molecularweight protein (Fr. I) in the cytosol of rat liver was not induced by injected metals, the threshold quantities of injected metals for the production of MT were evaluated from the ratios of metal content in the MT fraction to that in the Fr. I. The threshold doses of Cd, Hg and Zn for the production of MT were thus calculated as 0.30μg, 40μg and 100μg per rat, respectively, while Se did not induce MT. From these threshold doses, the amounts of metals in the liver required for the production of MT were estimated to be 0.193μg Cd, 1.7μg Hg and 7.4μg Zn per liver. From these results it could be presumed that the production of MT in the liver is initiated after the metal content in the liver reached a certain level.