Pulatova M K, Sharygin V L, Shliakova T G
Institute of Chemical Physics, Russian Academy of Sciences, Moscow, 119991 Russia.
Radiats Biol Radioecol. 2003 Jan-Feb;43(1):29-43.
The paper covers the problem on reactions of deoxyribonucleotide (dNTP) synthesis system in blood-forming organs of animals induced by irradiation. The synthesis of dNTP is a rate-limiting stage for DNA synthesis. Cellular requirements for dNTP pools during DNA synthesis are related with ensuring of the accuracy of DNA copying during replication and repair. It has been shown that organism defence mechanisms against irradiation include the following stages: 1. The prompt SOS-activation of dNTP synthesis 30 min later after irradiation, playing the important role in protecting of cell's genetic apparatus from damage. 2. The inhibition of dNTP synthesis within 3-24 h after irradiation resulting to the imbalance of four dNTP and the decrease of their pools. As result of that, the abnormal repair is observed due to depurinations, errors of base incorporations and "misrepair". 3. The restore of dNTP synthesis occurred 2 days later after irradiation. The increase of dNTP pools promotes the increase of DNA synthesis rate as well as proliferative activity of cells. Confirming the fact that the alterations in dNTP pools play essential role in the production of DNA lesions became an important step in understanding of the multistage process leading to radioprotection. To get high and balanced pools of dNTP needed for the increase in the volume of repair of DNA lesions the radioprotectors with high efficiency relative to the survival test were used in experiments. They induced the elevated dNTP synthesis in bone marrow and spleen during the time when the irradiation alone caused the essential prolonged suppression of dNTP synthesis as well as DNA and protein synthesis in organs of nonprotected animals. It has been shown that substances with antioxidant and antiradical activity induced the dNTP synthesis, too. In vivo regulatory factors of dNTP synthesis have been studied to elucidate the mechanisms of getting of high and balanced dNTP pools by using of different substances.
本文探讨了辐射诱导动物造血器官中脱氧核糖核苷酸(dNTP)合成系统的反应问题。dNTP的合成是DNA合成的限速阶段。DNA合成过程中细胞对dNTP库的需求与确保复制和修复过程中DNA复制的准确性有关。研究表明,机体对抗辐射的防御机制包括以下几个阶段:1. 照射后30分钟迅速激活dNTP合成的SOS反应,这在保护细胞遗传物质免受损伤方面发挥重要作用。2. 照射后3 - 24小时内dNTP合成受到抑制,导致四种dNTP失衡及其库容量减少。由此,由于脱嘌呤、碱基掺入错误和“错配修复”,观察到异常修复。3. 照射后2天dNTP合成恢复。dNTP库容量的增加促进了DNA合成速率以及细胞增殖活性的提高。证实dNTP库的变化在DNA损伤产生中起重要作用,这成为理解导致辐射防护的多阶段过程的重要一步。为了获得修复DNA损伤所需的高且平衡的dNTP库,实验中使用了相对于存活试验具有高效性的辐射防护剂。在单独照射导致未受保护动物器官中dNTP合成以及DNA和蛋白质合成显著长期抑制的时间段内,它们诱导骨髓和脾脏中dNTP合成升高。研究表明,具有抗氧化和抗自由基活性的物质也能诱导dNTP合成。为了阐明使用不同物质获得高且平衡的dNTP库的机制,对dNTP合成的体内调节因子进行了研究。