Inhibition of mammalian cell DNA synthesis by ionizing radiation.

Inhibition of mammalian cell DNA synthesis by ionizing radiation.
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电离辐射抑制哺乳动物细胞 DNA 合成。

DOI:
10.1080/09553008514552981
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发表时间:
1986
期刊:
International journal of radiation biology and related studies in physics, chemistry, and medicine
影响因子:
--
通讯作者:
R. Painter
R. Painter
中科院分区:
--
文献类型:
--
作者:
R. Painter

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电离辐射对正常哺乳动物细胞DNA合成速率的抑制作用的半对数图产生了一条双组分曲线。在低剂量时,陡峭成分的D0约为5GY,这是阻止DNA复制体启动的结果。较浅的成分,在高剂量时,D0大于或等于100GY,是阻止DNA链延长的结果。抑制DNA复制子起始的靶大小约为1000kb,抑制DNA链延长的靶大小约为50kb。有证据表明,这两种成分的靶标都只是DNA。因此,抑制DNA链延长的靶点大小与有效辐射诱导的DNA生长点前面的损伤以某种方式阻止其前进的想法是一致的。抑制DNA复制子起始的靶尺寸如此之大,以至于它必须包括许多复制子,这与复制子的大组(簇)中的任何一个单一病变足以阻止该复制子簇内所有复制子的复制起始的概念是一致的。对辐射敏感的人类细胞突变体的研究表明,存在一个中介因子,其正常功能是辐射诱导的损伤所必需的,从而导致抑制簇中复制子的启动和区块链的延长;该因子与聚(ADP-核糖)的合成无关。对辐射敏感的中国仓鼠细胞突变体的研究表明,双链断裂及其修复在调节辐射抑制复制子起始的持续时间方面是重要的,但与链延长的影响不大。电离辐射对DNA合成的抑制和对细胞的杀伤之间没有简单的联系。
A semi-log plot of the inhibitory effect of ionizing radiation on the rate of DNA synthesis in normal mammalian cells yields a two-component curve. The steep component, at low doses, has a D0 of about 5 Gy and is the result of blocks to initiation of DNA replicons. The shallow component, at high doses, has a D0 of greater than or equal to 100 Gy and is the result of blocks to DNA chain elongation. The target size for the inhibition of DNA replicon initiation is about 1000 kb, and the target size for inhibition of DNA chain elongation is about 50 kb. There is evidence that the target for both components is DNA alone. Therefore, the target size for inhibition of DNA chain elongation is consistent with the idea that an effective radiation-induced lesion in front of the DNA growing point somehow blocks its advance. The target size for inhibition of DNA replicon initiation is so large that it must include many replicons, which is consistent with the concept that a single lesion anywhere within a large group (cluster) of replicons is sufficient to block the initiation of replication of all replicons within that cluster. Studies with radiosensitive human cell mutants suggest that there is an intermediary factor whose normal function is necessary for radiation-induced lesions to cause the inhibition of replicon initiation in clusters and to block chain elongation; this factor is not related to poly(ADP-ribose) synthesis. Studies with radiosensitive Chinese hamster cell mutants suggest that double-strand breaks and their repair are important in regulating the duration of radiation-induced inhibition of replicon initiation but have little to do with effects on chain elongation. There is no simple correlation between inhibition of DNA synthesis and cell killing by ionizing radiation.
X 射线照射后同步 V-79 中国仓鼠细胞中染色体亚 DNA 的合成。
DOI: --
发表时间: 1984
期刊: Radiation research
影响因子: 3.4
作者:
Meechan,PJ;Carpenter,JG;Griffiths,TD
通讯作者: Griffiths,TD