Radioprotection of human cell nuclear DNA by polyamines: Radiosensitivity of chromatin is influenced by tightly bound spermine
Radioprotection of human cell nuclear DNA by polyamines: Radiosensitivity of chromatin is influenced by tightly bound spermine
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DOI：
10.2307/3579948
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发表时间：
1999-03-01
影响因子：
3.4
通讯作者：
Fahey, RC
中科院分区：
文献类型：
--
作者：
Warters, RL;Newton, GL;Fahey, RC
检测了多胺腐胺（PUT）和精胺（SPM）保护人细胞DNA免受辐射诱导的双链断裂（DSB）形成的能力。如前所述，在多胺几乎完全不存在的条件下，与核基质蛋白结合成类核，并组织成染色质结构，保护DNA不受DSB诱导，分别为4.5和95倍。在浓度低于1 mM时，PUT或SPM对脱蛋白核DNA提供了同等水平的保护，这与它们抑制辐射诱导的自由基的能力一致。在恒定的离子强度下，5ali SPM保护脱蛋白DNA和类核DNA以及核染色质中的DNA，分别为100和26倍。在5 mM SPM提供了15倍以上的保护脱蛋白的DNA比PUT。在生理相关的条件下，5 mM SPM保护完整细胞核中的DNA不受DSB诱导的影响，相对于在没有SPM的情况下的DNA为2倍。在细胞分级分离过程中SPM结合的研究表明，细胞SPM的显着部分是紧密结合在细胞核中，但可以通过延长洗涤去除。因此，SPM与核染色质的关联似乎是细胞DNA对DSB诱导的抗性的重要贡献者。(C)1999年，辐射研究协会。
The polyamines putrescine (PUT) and spermine (SPM) were examined for their ability to protect human cell DNA against the formation of radiation-induced double-strand breaks (DSBs), As observed previously, under conditions where polyamines were shown to be almost completely absent, association with nuclear matrix protein into a nucleoid, and organization into chromatin structure, protected DNA from induction of DSBs by factors of 4.5 and 95, respectively. At concentrations below 1 mM, PUT or SPM provided equivalent levels of protection to deproteinized nuclear DNA, consistent with their capacity to scavenge radiation-induced radicals. At constant ionic strength, 5 ali SPM protected deproteinized DNA and nucleoid DNA and DNA in nuclear chromatin by factors of 100 and 26, respectively. At 5 mM SPM provided 15 times greater protection of deproteinized DNA than did PUT. Under physiologically relevant conditions, 5 mM SPM protected DNA in the intact nucleus from the induction of DSBs by a factor of 2 relative to DNA in the absence of SPM. Studies of SPM binding during cellular fractionation revealed that a significant fraction of the cellular SPM is tightly bound in the nucleus but can be removed by extended washing. Thus the association of SPM with nuclear chromatin appears to be a significant contributor to the resistance of the cell's DNA to the induction of DSBs. (C) 1999 by Radiation Research Society.