1-beta-D-arabinofuranosylcytosine enhancement of resistance to several antineoplastic drugs in mammalian tissue culture cells.
This report describes the enhancement of drug resistance by 1-beta-D-arabinofuranosylcytosine at four individual loci and gene amplification at one locus in a hamster cell line. This drug has been used chemotherapeutically in the treatment of neoplasia and has documented effects on DNA synthesis. Our results in this paper demonstrate that the incidence of resistance to methotrexate, N-(phosphonoacetyl)-L-aspartate, and 5-fluoro-2'-deoxyuridine was appreciably increased after pretreatment with 1-beta-D-arabinofuranosylcytosine and they show that an increase in the incidence of gene amplification is one of the mechanisms by which drug resistance is increased. In contrast, the incidence of vincristine resistance was minimally enhanced by this drug. Possible reasons for this differential enhancement are discussed.
Goz
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Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill 27514.
Carl
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D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001221:Aspartate Carbamoyltransferase / Q000235:genetics; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000235:genetics; D002460:Cell Line; D006224:Cricetinae; D003561:Cytarabine / Q000494:pharmacology* / Q000633:toxicity; D004080:Dihydroorotase / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000187:drug effects*; D005467:Floxuridine / Q000494:pharmacology; D005784:Gene Amplification / Q000187:drug effects; D008727:Methotrexate / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000235:genetics; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014750:Vincristine / Q000494:pharmacology
D000964:Antimetabolites, Antineoplastic; C033626:CAD trifunctional enzyme; D009097:Multienzyme Complexes; D005467:Floxuridine; D003561:Cytarabine; D001224:Aspartic Acid; D014750:Vincristine; C013195:sparfosic acid; D001221:Aspartate Carbamoyltransferase; D004080:Dihydroorotase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing); D010746:Phosphonoacetic Acid; D008727:Methotrexate