The enhancement of the frequency of resistance to N-phosphonoacetyl-L-aspartate and methotrexate by 1-beta-D-arabinofuranosylcytosine: the effect of dipyridamole.
In cultured cells, dipyridamole, in a dose-dependent manner, prevented the enhancement by 1-beta-D-arabinofuranosylcytosine (AraC) of either N-phosphonoacetyl-L-aspartate (PALA)- or methotrexate- resistance frequency. Maximal blockade of enhancement of PALA-resistance frequency occurred if the dipyridamole was added with or within about 20 hr of PALA addition. Thereafter, the effect of dipyridamole decreased. Nitrobenzylthioinosine similarly reduced AraC enhancement of PALA- and methotrexate-resistance frequency. Both dipyridamole and nitrobenzylthioinosine inhibited uridine and thymidine uptake into cells to a similar extent in cells pretreated or not with AraC. Thus, although inhibition of nucleoside uptake would seem a reasonable explanation for the effect on PALA-resistance frequency by dipyridamole, there is no obvious explanation at present of how dipyridamole selectively affects resistance frequency in AraC-pretreated cells.
Goz
B
B
Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill.
Jeffs
L
L
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002461:Cell Line, Transformed; D006224:Cricetinae; D003561:Cytarabine / Q000494:pharmacology*; D004176:Dipyridamole / Q000494:pharmacology*; D004351:Drug Resistance; D004357:Drug Synergism; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology*; D009705:Nucleosides / Q000378:metabolism; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology
D009705:Nucleosides; D003561:Cytarabine; D001224:Aspartic Acid; D013868:Thioinosine; D004176:Dipyridamole; C013195:sparfosic acid; C001789:4-nitrobenzylthioinosine; D010746:Phosphonoacetic Acid; D008727:Methotrexate