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The role of methionine in methotrexate-sensitive and methotrexate-resistant mouse leukemia L1210 cells

  • Original Articles
  • Methionine, Methotrexate, L1210 Cells
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Summary

A mouse L1210 leukemia cell line was made 25-fold resistant to methotrexate (MTX) and had altered methionine transport and metabolism. L1210 cells resistant to methotrexate also had a 50-fold decrease in the exogenous methionine requirement for optimal cell growth compared to the parent cells. This change in methionine requirement was associated with differences in methionine metabolism between MTX-sensitive and MTX-resistant cell lines. Analysis of amino acid transport systems revealed different K1 and Vmax properties of methionine and nonmetabolizable amino acid analogues. There was a greater than twofold decrease in the initial sodium-dependent uptake of methionine in the resistant cells. Amino acid competition experiments revealed altered substrate specificities in the resistant cells. The cellular alterations occurring upon resistance may result from methotrexatemembrane interactions, and have been previously observed in cisplatinum-resistant cells. Thus modulation of methionine metabolism may provide the biochemical basis for MTX and cisplatinum collateral resistance.

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Authors and Affiliations

  1. Section of Biochemical Pharmacology, Department of Medical Oncology, City of Hope National Medical Center, 91010, Duarte, CA, USA

    Kevin J Scanlon, Mohammed Kashani-Sabet, Michele Pallai & Maria Saketos

  2. Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, 06510, New Haven, CT, USA

    Arlene R. Cashmore & Barbara A. Moroson

Authors
  1. Kevin J Scanlon
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  2. Mohammed Kashani-Sabet
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  3. Arlene R. Cashmore
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  4. Michele Pallai
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  5. Barbara A. Moroson
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  6. Maria Saketos
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Additional information

This work is supported by the American Cancer Society Grant (CH-265), USPHS CA 08010 and CA 16359, and the Chemotherapy Foundation, Inc.

Kevin J. Scanlon is a Scholar of the Leukemia Society of America

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Scanlon, K.J., Kashani-Sabet, M., Cashmore, A.R. et al. The role of methionine in methotrexate-sensitive and methotrexate-resistant mouse leukemia L1210 cells. Cancer Chemother. Pharmacol. 19, 25–29 (1987). https://doi.org/10.1007/BF00296250

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  • DOI: https://doi.org/10.1007/BF00296250

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