ALTERATION OF RIBONUCLEOTIDE REDUCTASE IN APHIDICOLIN-RESISTANT MUTANTS OF MOUSE FM3A CELLS WITH ASSOCIATED RESISTANCE TO ARABINOSYLADENINE AND ARABINOSYLCYTOSINE
ALTERATION OF RIBONUCLEOTIDE REDUCTASE IN APHIDICOLIN-RESISTANT MUTANTS OF MOUSE FM3A CELLS WITH ASSOCIATED RESISTANCE TO ARABINOSYLADENINE AND ARABINOSYLCYTOSINE
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DOI：
10.1007/bf01544746
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发表时间：
1981-01-01
期刊：
影响因子：
--
通讯作者：
SENO, T
中科院分区：
文献类型：
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作者：
AYUSAWA, D;IWATA, K;SENO, T
从小鼠乳腺癌细胞FM3A中分离并鉴定了抗阿霉菌素突变体。大多数突变株对阿拉伯糖基腺嘌呤、阿拉伯糖胞嘧啶、脱氧腺苷和过量胸腺嘧啶核苷表现出联合抗性。这种表型也可以在一个通过对低水平的阿拉伯糖胞嘧啶抗性而选择的变异系中观察到。在细胞-细胞杂交种中，抗性和交叉抗性表现为共显性性状。突变体的dATP池增加，将标记的脱氧胞苷结合到大分子中的能力降低。遗传和生化证据表明，赋予多效性表型的突变是由于核糖核苷酸还原酶活性的变化导致该酶对变构负效应dATP不敏感。这种酶的改变可能解释了脱氧核苷酸池的显着变化以及突变体对APHIPDICIN的抗性。
Aphidicolin-resistant mutants of mouse FM3A [mammary carcinoma] cells were isolated and characterized. Most of the mutants were of a type showing associated resistance to arabinosyladenine, arabinosylcytosine, deoxyadenosine and excess thymidine. This phenotype could also be observed in a variant line selected by resistance to a low level of arabinosylcytosine. In cell-cell hybrids, aphidicolin resistance and cross-resistance behaved as codominant traits. The mutants had an increased dATP pool and decrease ability to incorporate labeled deoxycytidine into macromolecules. Genetic and biochemical evidence suggested that the mutation conferring the pleiotropic phenotype resulted from a change in ribonucleotide reductase activity such that the enzyme was desensitized to the allosteric negative effector dATP. This alteration of the enzyme could account for the marked change in deoxynucleotide pools and for the aphidicolin resistance of the mutants.