Amplification of the metallothionein-I gene in cadmium-resistant mouse cells

Friend leukemia cells resistant to cadmium toxicity were selected. More than 70% of total cysteine incorporation in these cells was into the metal-binding protein, metallothionein. We used cDNA and genomic DNA clones containing the metallothionein-I gene to measure the concentration of its mRNA, the rate of gene transcription, and the number of genes. On a per cell basis, optimally induced, cadmium-resistant cells have a 14-fold more metallothionein-I mRNA, a 6-fold higher rate of metallothionein-I gene transcription, and 6-fold more metallothionein-I genes than do nonresistant cells. Metaphase spreads revealed that the resistant cells are nearly tetraploid and contain, on the average, three very small chromosomes that are absent from non-resistant Friend cells.