The activation of ribonucleotide reductase in animal organs as the cellular response against the treatment with DNA-damaging factors and the influence of radioprotectors on this effect.
Cellular requirements for deoxyribonucleotide (dNTP) pools during DNA synthesis are related to ensuring of the accuracy of DNA copying during replication and repair. This paper covers some problems on the reactions of dNTP synthesis system in organs of animals against the treatment with DNA-damaging agents. Ribonucleoside diphosphate reductase (NDPR) is the key enzyme for the synthesis of dNTP, since it catalyses the reductive conversion of ribonucleotides to deoxyribonucleotides. The results obtained show that the rapid and transient increase in NDPR activity in animal organs occurs as cellular response against the treatment with DNA-damaging agents (SOS-type activation). We have also found the intensive radioprotector-stimulated activation of deoxyribonucleotide synthesis as well as DNA and protein synthesis in mice organs within 3 days after the administration of two radioprotectors, indralin and indometaphen, that provide the high animal survival. Our studies suggest that these effects are the most important steps in the protective mechanism of the radioprotectors and are responsible for the high animal survival.
Pulatova
M K
MK
Semenov Institute of Chemical Physics, Russian Academy of Sciences, Kosygins str. 4, 117977, Semenov, Russia. pulatova@chph.ras.ru
Sharygin
V L
VL
Todorov
I N
IN
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects*; D003854:Deoxyribonucleotides / Q000096:biosynthesis; D004285:Dogs; D004578:Electron Spin Resonance Spectroscopy; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D051379:Mice; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D012264:Ribonucleotide Reductases / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014916:Whole-Body Irradiation
D003854:Deoxyribonucleotides; D010636:Phenols; D011837:Radiation-Protective Agents; C091454:indometafen; D013629:Tamoxifen; C086896:indralin; D012313:RNA; D012264:Ribonucleotide Reductases