[Reactions of deoxyribonucleotide synthesis system to irradiation and their modification by radioprotectors].
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.
Pulatova
M K
MK
Institute of Chemical Physics, Russian Academy of Sciences, Moscow, 119991 Russia. pulatova@chph.ras.ru
Sharygin
V L
VL
Shliakova
T G
TG
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001853:Bone Marrow / Q000378:metabolism; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004261:DNA Replication; D003854:Deoxyribonucleotides / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008962:Models, Theoretical; D010636:Phenols / Q000494:pharmacology; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000235:genetics / Q000378:metabolism*; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D013154:Spleen / Q000378:metabolism; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D024505:Tocopherols / Q000494:pharmacology
D000975:Antioxidants; D003854:Deoxyribonucleotides; D010636:Phenols; D011837:Radiation-Protective Agents; C091454:indometafen; D013629:Tamoxifen; C086896:indralin; D002084:Butylated Hydroxytoluene; D004247:DNA; D024505:Tocopherols