Goz B, Carl P L, Tlsty T D
Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill 27514.
Mol Pharmacol. 1989 Sep;36(3):360-5.
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.
本报告描述了在仓鼠细胞系中，1-β-D-阿拉伯呋喃糖基胞嘧啶在四个独立位点增强耐药性以及在一个位点发生基因扩增的情况。这种药物已被用于肿瘤化疗，并且已证明其对DNA合成有影响。我们在本文中的结果表明，用1-β-D-阿拉伯呋喃糖基胞嘧啶预处理后，对甲氨蝶呤、N-（膦酰基乙酰基）-L-天冬氨酸和5-氟-2'-脱氧尿苷的耐药发生率显著增加，并且结果表明基因扩增发生率的增加是耐药性增加的机制之一。相比之下，该药物对长春新碱耐药发生率的增强作用极小。文中讨论了这种差异增强的可能原因。
