TRANSIENT HYPOXIA ENHANCES THE FREQUENCY OF DIHYDROFOLATE-REDUCTASE GENE AMPLIFICATION IN CHINESE-HAMSTER OVARY CELLS
TRANSIENT HYPOXIA ENHANCES THE FREQUENCY OF DIHYDROFOLATE-REDUCTASE GENE AMPLIFICATION IN CHINESE-HAMSTER OVARY CELLS
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DOI：
10.1073/pnas.83.16.5978
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发表时间：
1986-08-01
影响因子：
11.1
通讯作者：
SCHIMKE, RT
中科院分区：
文献类型：
--
作者：
RICE, GC;HOY, C;SCHIMKE, RT
将中国仓鼠细胞暴露于降低的氧分压会导致甲氨蝶呤耐药性和二氢叶酸还原酶基因扩增的频率显着增强。增强的抗性的频率是（i）暴露于缺氧条件的长度和（ii）当细胞接种到含甲氨蝶呤的培养基中时从缺氧恢复后的时间的函数。缺氧导致DNA合成的抑制;在恢复到正常氧气气氛时，在缺氧开始时处于S期的细胞中> 60%随后在单个细胞周期内经历DNA的过度复制。具有增加的基因扩增频率的细胞来源于过度复制细胞的该子集。这些结果进行了讨论的背景下，许多实体瘤的缺氧状态和高频率的非整倍体，染色体畸变，和自发发生的耐药性的一些癌症化疗药物。
Exposure of Chinese hamster cells to reduced oxygen partial pressure results in a marked enhancement in the frequency of methotrexate resistance and dihydrofolate reductase gene amplification. The frequency of enhanced resistance is a function of (i) the length of exposure to hypoxic conditions and (ii) the time after recovery from hypoxia when cells are plated into methotrexate-containing medium. Hypoxia results in an inhibition of DNA synthesis; upon return to normal oxygen atmosphere, > 60% of cells in S phase at the time hypoxia was started subsequently undergo overreplication of DNA within a single cell cycle. The cells with the increased frequency of gene amplification are derived from this subset of overreplicated cells. These results are discussed within the context of the hypoxic state of many solid tumors and the high frequency of aneuploidy, chromosomal aberrations, and spontaneously occurring resistances to a number of cancer chemotherapeutic agents.