Lethal changes in bacteriophage DNA produced by x-rays.
Lethal changes in bacteriophage DNA produced by x-rays.
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X 射线产生的噬菌体 DNA 发生致命变化。
DOI：
10.2307/3583552
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发表时间：
1966
影响因子：
3.4
通讯作者：
D. Freifelder
中科院分区：
文献类型：
--
作者：
D. Freifelder
一般认为，辐射引起的微生物致命损伤的主要目标是DNA。本文将研究X射线在DNA中产生的一些结构变化，试图将它们与一种特殊的致死效应联系起来：即噬菌体在敏感宿主细菌中丧失自我繁殖的能力。这种系统的选择受到噬菌体结构相对简单的限制，并且到目前为止，它是唯一可以获得未被分离过程损伤的DNA的生物体。X射线引起的DNA分子损伤可分为三类：（1）主链损伤，如链断裂或糖残基中的化学作用;（2）碱基的改变或消除;（3）链内或链间类型或与蛋白质的交联。所有这些都已被观察到;问题是评估它们的相对生物学意义。这一问题的解决受到一个重要的理论难题--伴随问题的困扰。也就是说，化学显著性不一定保证生物相关性。然而，如果可以证明，在相同的辐照条件下，某些特定化学变化的产生速率与致死性损伤的积累速率相同，这是由存活曲线确定的，那么人们就可以合理地肯定地得出结论，这种化学变化就是致死性损伤。然而，应该记住，这种推理只是推论，而不是演绎。另一个明显而严重的问题是，许多化学变化可能会在细胞中得到修复，这可能会模糊观察到的原发性化学损伤与DNA中必须执行关键功能时实际存在的物质之间的关系。在试图检测生物学相关损伤时所经历的实验困难也不是小的，因为测量小损伤的问题。
It is generally accepted that the primary target for radiation-induced lethal damage in microorganisms is DNA. In the present paper some structural changes which are produced in DNA by X-rays will be investigated in an attempt to relate them to a particular lethal effect: that is, the loss of the ability of a bacteriophage to reproduce itself in a sensitive host bacterium. The choice of this system has been conditioned by the relative simplicity of the bacteriophage structure and by the fact that, up to the present, it is the only organism from which DNA undamaged by the isolation procedure can be obtained. The X-ray-induced damage suffered by DNA molecules may be classified into three categories: (1) main chain damage, such as strand breakage or chemical effects in the sugar residues; (2) alteration or elimination of bases; and (3) crosslinks of the intrastrand or interstrand type or to protein. All these have been observed; the problem is to assess their relative biological significance. The solution to this problem is beset by an important theoretical difficulty-the question of concomitance. That is, chemical prominence need not guarantee biological relevance. However, if it could be shown that, for identical conditions of irradiation, the rate of production of some particular chemical alteration is the same as the rate of accumulation of lethal hits, as determined from a survival curve, then one could with reasonable certainty conclude that the chemical change is the lethal lesion. However, it should be remembered that such reasoning is only inferential and not deductive. Another obvious and serious problem is that many chemical changes might be repaired in the cell which could obscure the relation between observed primary chemical lesions and what is actually in the DNA at the time when it must carry out a critical function. The experimental difficulties experienced in attempting to detect biologically relevant damage are also not minor because of the problem of measuring the small