Kinetics of metallothionein gene induction by cadmium in human lymphocytes

Induction of gene transcription is a complex process involving a diverse set of transcription factors and regulatory steps. We have taken a kinetic approach to analysis of metallothionein gene induction in human peripheral blood lymphocytes. By repeated measurements of MT mRNA after incubation of cells in vitro with CdCl2, we were able to determine individual-specific time related constants. The kinetics of induction for 3 individuals followed an S shaped curve and the data was fitted to a modified kinetic model of gene transcription. From this model, which assumes a cooperativity effect, transcriptional and RNA degradation rate constants could be calculated. The rate constant for transcription was doubled with the doubling of CdCl2 concentration, but the rate constant for RNA degradation was independent of Cd concentration.