Bridges B A
Ciba Found Symp. 1980;76:67-81. doi: 10.1002/9780470720592.ch5.
Three phenomena examined here have been claimed to reflect the operation of inducible repair systems. It has been postulated that 'SOS repair' involves the induction by DNA-damaging agents of an error-prone repair system that is capable of affecting the replication of damaged DNA. This system works with bacteriophages and animal viruses, in which it is possible to separate the effects of DNA damage on the viral DNA from that on the host cell. Whether this system also operates in repair of the cell's own DNA is, however, controversial. The system appears to have little effect on survival of bacterial cells and its operation in cellular mutagenesis is still not proven, at least in bacteria with otherwise normal repair capacity. 'Adaptation' is the response of bacteria to low doses of methylating agents. Adapted bacteria are more resistant to the lethal and mutagenic action of alkytlating agents. The process includes the induction of an enzyme that 'removes' O6-alkylated bases from DNA and which, unusually, is consumed during the course of the reaction. The reaction itself is also unknown; it does not depend on a nuclease, glycosylase or demethylase, but could use a transmethylase. There is some evidence that an analogous process occurs in animals. The third process affects the synthesis of high molecular weight DNA in cultured mammalian cells that have been exposed to split doses of DNA-damaging agents. It has been postulated that this system is inducible and error-free, but detailed analysis suggests that the observed effect is an artifact arising from an abnormal distribution of sizes of nascent DNA after the second dose, and as a result of exposure to the first dose. Inducible DNA repair systems may be expected to influence kinetics of the dose--response relationships obtained after exposure of cells to mutagens and carcinogens. The interactions between these effects and those produced by inducible pathways of metabolic activation and detoxification are discussed.
这里所研究的三种现象据称反映了诱导性修复系统的作用。据推测，“SOS修复”涉及DNA损伤剂诱导产生一种易出错的修复系统，该系统能够影响受损DNA的复制。这个系统作用于噬菌体和动物病毒，在这些病毒中，可以将DNA损伤对病毒DNA的影响与对宿主细胞的影响区分开来。然而，这个系统是否也在细胞自身DNA的修复中起作用仍存在争议。该系统似乎对细菌细胞的存活影响很小，其在细胞诱变中的作用尚未得到证实，至少在具有正常修复能力的细菌中是这样。“适应性”是细菌对低剂量甲基化剂的反应。适应性细菌对烷基化剂的致死和诱变作用更具抗性。这个过程包括诱导一种能从DNA中“去除”O6 - 烷基化碱基的酶，而且不同寻常的是，该酶在反应过程中会被消耗。反应本身也不清楚；它不依赖于核酸酶、糖基化酶或脱甲基酶，但可能利用转甲基酶。有一些证据表明动物中也发生类似的过程。第三个过程影响暴露于分次剂量DNA损伤剂的培养哺乳动物细胞中高分子量DNA的合成。据推测，这个系统是可诱导且无差错的，但详细分析表明，观察到的效应是由于第二次剂量后新生DNA大小异常分布以及第一次剂量暴露导致的假象。诱导性DNA修复系统可能会影响细胞暴露于诱变剂和致癌物后获得的剂量 - 反应关系的动力学。本文讨论了这些效应与代谢活化和解毒的诱导途径所产生的效应之间的相互作用。
