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Molecular Pharmacology

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Research ArticleArticle

Low Specificity of the Nucleoside Transport Mechanism of RPMI 6410 Cells

ALAN R. P. PATERSON, SUH-ER YANG, EDA Y. LAU and CAROL E. CASS
Molecular Pharmacology November 1979, 16 (3) 900-908;
ALAN R. P. PATERSON
Cancer Research Unit (McEachern Laboratory) and Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
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SUH-ER YANG
Cancer Research Unit (McEachern Laboratory) and Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
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EDA Y. LAU
Cancer Research Unit (McEachern Laboratory) and Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
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CAROL E. CASS
Cancer Research Unit (McEachern Laboratory) and Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
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Abstract

The toxic effects of various nucleoside antimetabolites toward RPMI 6410 cells in culture were eliminated or reduced when the growth medium contained 5 µM nitrobenzylthioinosine (NBMPR), a potent inhibitor of nucleoside transport. When cells were "protected" in this way from the growth inhibitory effects of trifluorothymidine, arabinosylcytosine or 6-azauridine, the cellular content of these agents was much reduced relative to that of cells cultured in the absence of NBMPR, indicating that NBMPR impairment of nucleoside transport was the basis of the protective effect. It is implicit in these results that the toxic nucleosides against which protection is afforded by NBMPR are "substrates" for the nucleoside transporter. The cytotoxic effects of a number of nucleosides of diverse structure were ameliorated by NBMPR and these compounds were judged to be substrates for the transporter. Because compounds as diverse as showdomycin, 5-azacytidine, sangivamycin and nebularine were permeants by this criterion, it was concluded that the specificity of the nucleoside transport mechanism of RPMI 6410 cells is low with respect to the base portion of nucleosides.

ACKNOWLEDGMENT For the provision of nucleosides we are grateful to the Division of Cancer Treatment, National Cancer Institute, Bethesda, Md. and to the following investigators: A. Bloch, T. A. Khwaja, G. A. LePage, J. A. Montgomery, Y. F. Shealy, M. J. Sweeney, L. B. Townsend, and H. Umezawa.

  • Copyright © 1979 by Academic Press, Inc.

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Molecular Pharmacology
Vol. 16, Issue 3
1 Nov 1979
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Research ArticleArticle

Low Specificity of the Nucleoside Transport Mechanism of RPMI 6410 Cells

ALAN R. P. PATERSON, SUH-ER YANG, EDA Y. LAU and CAROL E. CASS
Molecular Pharmacology November 1, 1979, 16 (3) 900-908;

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Research ArticleArticle

Low Specificity of the Nucleoside Transport Mechanism of RPMI 6410 Cells

ALAN R. P. PATERSON, SUH-ER YANG, EDA Y. LAU and CAROL E. CASS
Molecular Pharmacology November 1, 1979, 16 (3) 900-908;
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