Effects of hydroxyurea and 1-beta-D-arabinofuranosyl-cytosine on deoxyribonucleotide pools in mouse embryo cells.
Effects of hydroxyurea and 1-beta-D-arabinofuranosyl-cytosine on deoxyribonucleotide pools in mouse embryo cells.
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羟基脲和 1-β-D-阿拉伯呋喃糖基-胞嘧啶对小鼠胚胎细胞脱氧核糖核苷酸池的影响。
DOI：
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发表时间：
1971
期刊：
影响因子：
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通讯作者：
B. Nordenskjöld
中科院分区：
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作者：
Lambert Skoog;B. Nordenskjöld
在含有0.5%血清的培养基中孵育的小鼠胚胎细胞仅含有少量合成DNA的细胞。当血清浓度升高时，DNA合成被诱导，脱氧核苷三磷酸的池扩大。在这样的培养物中，dGTP池是脱氧核糖核苷三磷酸池中最小的，其大小仅对应于约30秒的DNA合成。dCTP池比dGTP池大10-20倍。
加入羟基脲导致dGTP池几乎瞬间损失，并且dATP池的大小也减少。相反，dCTP和dTTP池增加。然而，dTTP池的周转率大大降低。
从培养基中去除羟基脲导致三磷酸池快速正常化，但仅导致DNA合成的更逐渐恢复。
在1-β-D-阿拉伯呋喃糖基-胞嘧啶（阿拉伯糖基-胞嘧啶）中孵育期间，dATP、dGTP和dTTP池扩增，而dCTP池显示初始减少。尽管DNA合成大大减少，但dTTP池的营业额没有受到明显影响。当去除阿糖胞苷时，池被标准化，DNA合成缓慢恢复。
因此，我们的研究结果表明，DNA合成的抑制与减少池的dGTP和dATP和dTTP的营业额减少，表明一般减少脱氧核糖核苷酸的形成，大概是由于抑制酶核糖核苷二磷酸还原酶。阿糖胞苷对DNA合成的抑制作用与脱氧核苷三磷酸池的类似耗竭无关。
Mouse embryo cells incubated in medium with 0.5% serum contain only few cells which synthesize DNA. When the serum concentration was raised, DNA synthesis was induced and the pools of the deoxyribonucleoside triphosphates expanded. In such cultures the pool of dGTP was the smallest of the deoxyribonucleoside triphosphate pools and its size corresponded to only approximately 30 sec of DNA synthesis. The dCTP pool was 10–20 times larger than the dGTP pool.
Addition of hydroxyurea resulted in an almost instantaneous loss of the pool of dGTP and also in a decrease in the size of the dATP pool. In contrast the pools of dCTP and dTTP increased. However, the turnover of the dTTP pool was greatly diminished.
Removal of hydroxyurea from the medium resulted in a rapid normalization of the triphosphate pools but only in a more gradual restoration of DNA synthesis.
During incubation in 1-β-D-arabinofuranosyl-cytosine (arabinosyl-cytosine), the pools of dATP, dGTP and dTTP expanded, while the pool of dCTP showed an initial decrease. The turnover of the dTTP pool was not markedly affected in spite of the fact that DNA synthesis was greatly reduced. When arabinosyl-cytosine was removed the pools were normalized and DNA synthesis was slowly restored.
Our results thus show that the inhibition of DNA synthesis by hydroxyurea is correlated with diminishing pools of dGTP and dATP and a decreased turnover of dTTP, indicating a generally decreased deoxyribonucleotide formation presumably due to the inhibition of the enzyme ribonucleoside-diphosphate reductase. The inhibition of DNA synthesis by arabinosyl-cytosine is not correlated with a similar depletion of deoxyribonucleoside triphosphate pools.