Acute treatment of mice with cadmium salts results in amplification of the metallothionein-1 gene in liver.

A variety of genes have been shown to change copy number during development, including rRNA genes in amphibians and chorion proteins in insects. Dihydrofolate reductase and metallothionein-1 (MT-1) genes are present in high copy number in cultured mammalian cells subjected to low levels of agents that will select for cells with amplified copies of specific genes. Recent studies have shown that the metallothionein-1 gene in mouse liver is regulated at the transcriptional level by treatment with heavy metals. We report here that, at cadmium concentrations 5 to 10-fold higher than that required to induce maximal transcription of the MT-1 gene, there is a 2 to 3-fold increase in MT-1 gene concentration in liver nuclear DNA by 6 hours after induction, and extra copies persist up to 3 weeks in the absence of further heavy metal treatment. The extra MT-1 gene copies that appear 6 hours after cadmium treatment are in a conformation that renders them relatively nuclease insensitive.