Studies on 1-β-D-arabinofuranosyl cytosine-resistant mutants of Chinese hamster fibroblasts: III. Joint resistance to arabinofuranosyl cytosine and to excess thymidine—A semidominant manifestation of deoxycytidine triphosphate pool expansion
Studies on 1-β-D-arabinofuranosyl cytosine-resistant mutants of Chinese hamster fibroblasts: III. Joint resistance to arabinofuranosyl cytosine and to excess thymidine—A semidominant manifestation of deoxycytidine triphosphate pool expansion
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中国仓鼠成纤维细胞1-β-D-阿拉伯呋喃糖基胞嘧啶抗性突变体的研究：三、阿拉伯呋喃糖基胞嘧啶和过量胸苷的联合抗性——脱氧胞苷三磷酸池扩张的半显性表现
DOI：
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发表时间：
1979
期刊：
影响因子：
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通讯作者：
G. Buttin
中科院分区：
文献类型：
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作者：
B. Robert De Saint Vincent;G. Buttin
通过暴露于阿糖胞苷的单循环从诱变的中国仓鼠成纤维细胞分离的变体分为两类：（1）具有高水平抗性的脱氧胞苷（dC）激酶缺陷型克隆，该表型在杂交种中是隐性的;和（2）对胸苷（dT）和“低”阿糖胞苷浓度表现出联合抗性的克隆，该表型由增加的dCTP库解释。在这些变体中，外源性dC掺入大分子中显着改变。在杂种中，对dT和ara-C的联合抗性表现为半显性。通过第二次选择步骤，恢复了对阿糖胞苷的隐性高抗性和半显性dT抗性累积的变体。这两类ara-C耐药变异体的鉴定表明，已知的ara-C耐药表型解释为染色体基因突变的表现。显性耐药突变可能有助于长期阿糖胞苷化疗期间癌细胞的存活。
Variants isolated from mutagenized Chinese hamster fibroblasts by a single cycle of exposure to ara-C distributed into two classes: (1) deoxycytidine (dC) kinase deficient clones with a high level of resistance, this phenotype was recessive in hybrids; and (2) clones exhibiting joint resistance to thymidine (dT) and to “low” ara-C concentration, this phenotype was accounted for by an increased dCTP pool. The incorporation of exogenous dC into macromolecules was markedly altered in these variants. In hybrids, the phenotype of joint resistance to dT and ara-C was semidominant. Through a second selection step, variants cumulating recessive high resistance to ara-C and semidominant dT resistance were recovered. The identification of these two classes of ara-C-resistant variants suggests an interpretation of the known phenotypes of ara-C resistance as manifestations of chromosomal gene mutations. Dominant resistance mutations might contribute to the survival of cancer cells during prolonged ara-C chemotherapy.