Nucleic Acids Research, 1985, Vol. 13, No. 15 5423-5439
© 1985
Articles |
Acute treatment of mice with cadmium salts results in amplification of the metallothlonein-1 gene in liver
London Regional Cancer Centre 391 South Street, London, Ontario N6A 4G5 1Department of Biology, University of Calgary Calgary, Alberta T2N 1N4, Canada
*To Whom reprint requests should be sent
Received June 13, 1985. Accepted July 3, 1985.
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 metallothlonein-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.