Models for thiol protection of DNA in cells.
Models for thiol protection of DNA in cells.
复制标题
细胞中 DNA 硫醇保护模型。
DOI：
10.1016/0163-7258(88)90050-2
复制
发表时间：
1988
影响因子：
13.5
通讯作者：
Held,KD
中科院分区：
文献类型：
--
作者：
Held,KD
人们普遍认为，电离辐射导致的细胞死亡主要是由于 DNA 损伤造成的，尽管两个终点之间的确切关系尚不清楚。此外，通过添加硫醇来改变DNA损伤与改变细胞杀伤之间的关系尚不清楚。各种模型已被用来研究 DNA 损伤以及硫醇对其的影响。这些包括 DNA 成分的辐射化学研究、溶液中辐照 DNA 的物理损伤（如链断裂和交联产生）、溶液中辐照 DNA 的生物活性以及辐照细胞 DNA 的物理损伤。比较这些不同研究中获得的结果并从它们推断细胞杀伤是困难的，至少部分是因为经常使用非常不同的辐射条件（例如剂量、剂量率、缓冲液、pH、硫醇化合物等）。在过去的几年中，我们使用许多系统对硫醇进行了研究：DNA成分的脉冲放射分解（Held等人，1985）、细菌转化DNA的生物活性（Held等人，1981、1984a、b）、哺乳动物细胞中的DNA链断裂（Held等人，1986）和哺乳动物细胞杀伤（Held，1985）。在所有这些研究中，都使用了硫醇化合物二硫苏糖醇（DTT），这应该有助于从一个系统到下一个系统进行比较和外推。本文将回顾这些研究，并与其他相关文献进行比较，试图解决以下问题：DNA 是否是辐射诱导细胞杀伤的硫醇修饰的“目标”？已经提出了许多不同的假设来解释含硫醇化合物的辐射防护作用。这些已经在之前列出和讨论过（例如，Klayman 和 Copeland，1975），包括通过硫醇清除 OH 自由基；硫醇向辐射诱导的有机自由基提供氢原子，与这些自由基与氧的反应竞争[修复固定模型（Alexander 和 Charlesby，1955）]；通过氧化硫醇诱导缺氧（例如 Durand，1983）；金属螯合；和二硫化物的产生。要解决的第二个问题是 DNA 保护是否可以通过与所提供的数据相关的这些不同假设来解释，特别强调前两个假设。
It is generally assumed that death of a cell from exposure to ionizing radiation results primarily from damage to DNA, although the exact relationship between the two endpoints is not clear. Furthermore, the relationship between modification of DNA damage by the addition of thiols and modification of cell killing is not understood. Various models have been used to study DNA damage and the effects of thiols on it. These include studies of radiation chemistry of DNA constituents, physical damage such as strand break and crosslink production in DNA irradiated in solution, biological activity of DNA irradiated in solution, and physical damage in DNA from irradiated cells. It is difficult to compare the results obtained in these various studies and to extrapolate from them to cell killing, in part at least, because very different radiation conditions (eg dose, dose rate, buffer, pH, thiol compound, etc.) are often used. Over the past several years we have performed studies with thiols using a number of systems: pulse radiolysis of DNA constituents (Held et al., 1985), biological activity of bacterial transforming DNA (Held et al., 1981, 1984a, b), DNA strand breaks in mammalian cells (Held et al., 1986), and mammalian cell killing (Held, 1985). In all these studies the thiol compound dithiothreitol (DTT) was used, and this should help in making comparisons and extrapolations from one system to the next. In this paper these studies will be reviewed and compared with other relevant literature in an attempt to address the question: Is DNA the'target'for thiol modification of radiation-induced cell killing?A number of different hypotheses have been proposed to account for radioprotection by thiolcontaining compounds. These have been listed and discussed previously (eg Klayman and Copeland, 1975) and include OH radical scavenging by thiols; hydrogen atom donation from thiols to radiation-induced organic free radicals in competition with reaction of those radicals with oxygen [the repair-fixation model (Alexander and Charlesby, 1955)]; hypoxia induction by oxidizing thiols (eg Durand, 1983); chelation of metals; and production of disulfides. The second question to be addressed is whether DNA protection can be explained by these various hypotheses in relation to the data presented, with particular emphasis given to the first two hypotheses.