Organization and Amplification of Metallothionein Genes in Eukaryotic Cells

Abstract

Metallothioneins (MTs) are low molecular weight, cysteine-rich metal-binding proteins. In mammalian organisms, human MT genes are present as multigene families. Amplification of eukaryotic MT genes has been described in cellular systems ranging from yeasts to human. The authors also are indebted to the numerous collaborators, whose work is cited herein, who have contributed to the studies of cadmium resistance and MT gene amplification in mammalian cell lines over the course of the past 15 years. Molecular analysis of human MT gene sequences via quantitative DNA spot blotting and Southern gel transfer revealed approximately four- to fivefold amplification of all expected fragments of the functional human MT gene cluster. Mouse variant cell lines derived from a Cd-sensitive Friend erythroleukemia cell line selected by stepwise increases in Cd concentration in growth medium showed approximately 14-fold increased expression of MT mRNA and a 6-fold increase in MT I gene copy number.