Effect of cycloheximide on the induction of metallothionein and acute toxicity of cadmium in mice.

Abstract

Using male mice of ICR strain, the effect of cycloheximide on metal-lothionein production and the acute toxicity of Cd were studied. Followiug ad-ministration of Cd alone (2.5 mg/kg body weight), most of the Cd accumulated in the lives and kidney was found in the metallothionein (MT) region. Zn was also detected in this region, being enhanced with increasing time after Cd injection. Following combined treatment with Cd and cycloheximide (total dose 2.0 mg), the proportions of Cd and Zn in the cell sap were slightly decreased. In the MT region, the proportion of Cd was markedly decreased by cycloheximide. In par-ticular, in the Cd + Cy-10 hr group, this proportion in the liver and kidney was half of that in the Cd-10 hr group treated with Cd only. The proportion of Cd increased at 24 hr after Cd injection, even though the mice were treated with cycloheximide. Simultaneously, the proportion of Zn in the MT region also in-creased. Mice injected with 2.5 mg Cd/kg body weight did not die up to 24 hr after this metal injection. Following the combined treatment with Cd and cycloheximide, however, 6 out of 10 mice died within 24 hr after Cd injection. These results suggest that the toxicity of Cd is modified by cycloheximide, and MT synthesis contributes to the appearance of this toxicity.