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Expression of a methotrexate-resistant dihydrofolate reductase gene by transformed hematopoietic cells of mice

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Somatic Cell Genetics

Abstract

DNA-mediated gene transfer was used to introduce DNA from a methotrexate-resistant mouse fibroblast cell line into mouse bone marrow cells. This cell line contained a methotrexate-resistant dihydrofolate reductase, active at 10−4 M methotrexate, which was electrophoretically separable from the wild-type mouse enzyme. Transformed hematopoietic cells were returned to irradiated mice and selected in vivo by methotrexate administration. Some recipients of transformed marrow cells expressed the electrophoretically distinct, methotrexate-resistant dihydrofolate reductase in hematopoietic cells. These observations suggest that successful transformation of marrow stem cells to methotrexate resistance is accomplished by insertion of a dihydrofolate reductase gene coding for a mutant enzyme that is highly resistant to methotrexate.

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Authors and Affiliations

  1. Division of Hematology-Oncology and the Jonsson Comprehensive Cancer Center, UCLA School of Medicine, 90024, Los Angeles, California

    M. Bar-Eli, H. D. Stang, K. E. Mercola & M. J. Cline

Authors
  1. M. Bar-Eli
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  2. H. D. Stang
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  3. K. E. Mercola
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  4. M. J. Cline
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Bar-Eli, M., Stang, H.D., Mercola, K.E. et al. Expression of a methotrexate-resistant dihydrofolate reductase gene by transformed hematopoietic cells of mice. Somat Cell Mol Genet 9, 55–67 (1983). https://doi.org/10.1007/BF01544048

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  • DOI: https://doi.org/10.1007/BF01544048

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