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Science 8 December 1978:
Vol. 202. no. 4372, pp. 1051 - 1055
DOI: 10.1126/science.715457
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Articles

Science, Vol 202, Issue 4372, 1051-1055
Copyright © 1978 by American Association for the Advancement of Science

articles

Gene amplification and drug resistance in cultured murine cells

RT Schimke, RJ Kaufman, FW Alt, and RF Kellems

Resistance of mouse cells to the folate analog, methotrexate, results from selection of increasingly resistant cells on progressive increases of methotrexate in the culture medium. High-level resistance is associated with high rates of synthesis of dihydrofolate reductase and correspondingly high numbers of reductase genes. In some variants high resistance and gene copy number are stable in the absence of selection pressure, whereas in others they are unstable. Analogies are made to antibiotic and insecticide resistance wherein selection of organisms with increased capacity to counteract the drug effect results in emergence of resistance. Gene amplification may underlie many such resistance phenomena.


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