Increased synthetic capacity for metallothionein in cultured liver cells following dimethyl sulfoxide pretreatment

Abstract

Cultured TRL 1215 cells in log phase of growth were exposed to dimethyl sulfoxide (DMSO; 14-280 mM) followed 48 h later by cadmium (10 μm). Intracellular concentrations of metallothionein (MT) were measured 24 h after cadmium addition. Cadmium alone caused a 10-fold increase in the levels of MT, while DMSO alone had no effect on cellular MT levels. DMSO pretreatment followed by cadmium exposure, however, resulted in MT levels that were elevated by a factor of as much as 25-fold those observed in control cells. Concurrent treatment with the DNA synthesis inhibitor hydroxyurea (HU) eliminated the enhancing effect of DMSO pretreatment on cadmium induction of MT, indicating the requirement of DNA synthesis. An enhancement of the cellular accumulation of the metal ion did not account for the increased cadmium-induced MT synthesis in DMSO-pretreated cells as these cells did not show significantly increased uptake of cadmium during the initial period of exposure. DMSO pretreatment enhances cadmium induction of MT synthesis through a mechanism that appears to be dependent on the synthesis of DNA.