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. 1981 Dec;1(12):1084–1093. doi: 10.1128/mcb.1.12.1084

Loss and stabilization of amplified dihydrofolate reductase genes in mouse sarcoma S-180 cell lines.

R J Kaufman, P C Brown, R T Schimke
PMCID: PMC369735  PMID: 7346713

Abstract

We studied the loss and stabilization of dihydrofolate reductase genes in clones of a methotrexate-resistant murine S-180 cell line. These cells contained multiple copies of the dihydrofolate reductase gene which were associated with double minute chromosomes. The growth rate of these cells in the absence of methotrexate was inversely related to the degree of gene amplification (number of double minute chromosomes). Cells could both gain and lose genes as a result of an unequal distribution of double minute chromosomes into daughter cells at mitosis. The loss of amplified dihydrofolate reductase genes during growth in the absence of methotrexate resulted from the continual generation of cells containing lower numbers of double minute chromosomes. Because of the growth advantage of these cells, they became dominant in the population. We also studied an unstably resistant S-180 cell line (clone) that, after 3 years of continuous growth in methotrexate, generated cells containing stably amplified dihydrofolate reductase genes. These genes were present on one or more chromosomes, and they were retained in a stable state.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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