Increased gene amplification in L5178Y mouse lymphoma cells with hydroxyurea-induced chromosomal aberrations.

Increased gene amplification in L5178Y mouse lymphoma cells with hydroxyurea-induced chromosomal aberrations.
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发表时间:
1985-10
期刊:
影响因子:
11.2
通讯作者:
A. Hill;R. Schimke
A. Hill;R. Schimke
中科院分区:
医学1区
文献类型:
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作者:
A. Hill;R. Schimke

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羟基脲治疗后,L5178Y小鼠淋巴瘤细胞出现染色体畸变和二氢叶酸还原酶基因扩增。畸变的类型包括多倍体、内重复、染色体断裂和染色体外DNA的存在。通过细胞分选分析羟基脲处理的细胞显示,细胞亚群DNA增加,二氢叶酸还原酶增加。该亚群显示染色体畸变发生率高,二氢叶酸还原酶基因扩增频率增加。脱氧核糖核酸和二氢叶酸还原酶含量正常的羟基脲处理细胞畸变少,二氢叶酸还原酶基因扩增频率低。我们认为羟基脲处理会导致DNA的过度复制,而过度复制的DNA的重组会导致染色体畸变和基因扩增。
Chromosomal aberrations and dihydrofolate reductase gene amplification are observed in L5178Y mouse lymphoma cells after treatment with hydroxyurea. The types of aberrations include polyploidy, endoreduplication, chromosome fragmentation, and the presence of extrachromosomal DNA. Hydroxyurea-treated cells analyzed by cell sorting showed a subpopulation of cells with increased DNA and increased dihydrofolate reductase. This subpopulation shows a high incidence of chromosome aberrations and an increased frequency of dihydrofolate reductase gene amplification. Hydroxyurea-treated cells with the normal amount of DNA and dihydrofolate reductase have few aberrations and a low frequency of dihydrofolate reductase gene amplification. We propose that hydroxyurea treatment causes overreplication of DNA and that recombination of overreplicated DNA can lead to chromosome aberrations and gene amplification.