PMID: 9551083Apr 29, 1998Paper

Selection and characterisation of murine leukaemia L1210 cells with high-level resistance to the cytostatic activity of the acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl) adenine (PMEA)

Biochimica Et Biophysica Acta
J BalzariniE De Clercq

Abstract

An L1210 cell line showing a 300-fold resistance to the cytostatic effect of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) (designated L1210/PMEA-1) was selected in cell culture upon exposure of wild-type L1210/0 cells to stepwise-increased drug concentrations. The mutant L1210/PMEA-1 cell line was characterized by an unusual specificity in that the cytostatic activity was severely impaired only for PMEA and the closely related 2,6-diaminopurine derivative PMEDAP, but not for its guanine counterpart PMEG or for 9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA). The L1210/PMEA-1 cell line showed poor resistance to the cytostatic activity of the lipophilic PMEA prodrug bis(POM)PMEA and virtually kept its PMEA resistance profile in the presence of indomethacin, excluding resistance of the cells of PMEA and PMEDAP by an increased efflux of the drugs. Intracellular purine nucleotide pool labelling studies with adenine, hypoxanthine and glycine revealed that PMEA/PMEDAP resistance did not originate from a defect in the enzymatic pathways of purine nucleotides. ATP, AMP and cAMP, but not adenosine, adenine, HPMPA and inhibitors of nucleoside transport carriers markedly interfered with PMEA uptake in L1210/0 cells. The L1210/PMEA-1 c...Continue Reading

References

Feb 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·J BalzariniE De Clercq
Jun 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·J BalzariniE De Clercq
Jul 1, 1991·Antiviral Research·G PalúE De Clercq
Jan 1, 1990·Annals of the New York Academy of Sciences·J J BronsonM J Hitchcock
Apr 1, 1989·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·W S DaltonS E Salmon
Jul 1, 1988·Antimicrobial Agents and Chemotherapy·R PauwelsE De Clercq
Oct 2, 1986·Nature·E De ClercqP C Maudgal
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·G J ZamanH J Broxterman

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Citations

Nov 9, 2002·AAPS PharmSci·J SampathJ D Schuetz
Aug 5, 1999·Nucleosides & Nucleotides·E De ClercqR Snoeck
Jul 20, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Aravind Basavapathruni, Karen S Anderson

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