Enhancement of cadmium-induced metallothionein synthesis in cultured TRL 1215 cells by butyric acid pretreatment.

Cultured TRL 1215 cells in log phase of growth were exposed first to butyric acid (BA; 0.1-2.0 mM) and then 48 h later, to cadmium (Cd; 10 microM). Metallothionein (MT) concentrations were measured 24 h after Cd addition. Cd alone caused approx. a 10-fold increase in cellular MT levels, while BA alone had no effect. BA pretreatment followed by Cd exposure, however, resulted in MT levels up to 25 times those in control cells. Concurrent exposure to hydroxyurea (HU) eliminated the enhancing effect of BA pretreatment on induction of MT by Cd, indicating that DNA synthesis is required. BA-pretreated cells did not show marked increases in cellular uptake of Cd. BA pretreatment enhances Cd induction of MT synthesis through a mechanism that is dependent on the synthesis of DNA.