[Time- and dose-dependent post-irradiation changes of Fe3+-transferrin and Cu2+-ceruloplasmin pools in blood, their influence on ribonucleotide reductase activity in animal tissues and the effects of radioprotectors].

The time- and dose-dependent changes of Fe(3+)-transferrin (Fe(3+)-TF) and Cu(2+)-ceruloplasmin (Cu(2+)-CP) pools, of superoxide dismutase activity and the inhibitory activity of alpha 2-macroglobulin in blood as well as changes in synthesis rates of deoxyribonucleotides (dNTP), DNA and proteins in organs (spleen, liver, bone marrow, thymus) of mice and dogs given total body irradiation have been studied using of ESR spectroscopy, radioisotope techniques and biochemical determination of enzymatic activity. The experimental data have allowed us to reveal the sequence of organism's response reactions against irradiation and their modifications by radioprotectors. Changes in blood Fe(3+)-TF pool is one of the most informative, highly radiosensitive and rapidly reactive marker against irradiation and drug administrations. This irontransport protein controls a rate-limiting iron-dependent stage for DNA synthesis--the synthesis of dNTP, catalyzed by iron-containing ribonucleotide reductase (Fe(3+)-RR). It has been shown that time-dependent post-irradiation changes of Fe(3+)-TP pool in blood are characterized by three distinct stages: 1) the prompt increase of pool (SOS-type response) playing the important role in protecting of cell's genetic apparatus from damage; 2) the decrease of its pool within 3-18 h after irradiation resulting in the loss of Fe(3+)-RR activity in tissues of blood-forming organs that make more stronger radiation-induced damage; 3) the following phase-dependent increase in Fe(3+)-TF pool at the 2-nd, 6th, 10-17th days after irradiation due to an increase in transferrin synthesis. This increase may be considered as compensatory reaction of blood-forming organs directed at restoring blood and organ's cells. The time-dependent courses of the reactions are independent from radiation doses indicating to the universal and nonspecific response of organism against irradiation. But, the intensity of this compensatory-adaptive response at 2-nd and 6th days grows with increasing radiation dose up to lethal that, and organism's response becomes abnormal and physiologically hypertrophic. The prolonged "stressful syndrome of biochemical tense state" should be attributed to negative effects for organism, since it may result in the failure of compensatory adaptive organism's reactions and animal killing. The radioprotectors ward off the appearance of this dangerous state. Dogs with initial individual characteristics of blood which were typical for "suppressed" or "activated" states had abnormal response against irradiation by low doses 0.25 or 0.5 Gy. In these cases the intensity of response reactions of organism was essentially increased and markedly deviated from linear dose dependence. The phase-dependent increase of Fe(3+)-TF pool in blood in post-irradiation time resulted to the increase of Fe(3+)-RR activity in blood-forming organs. The key event ensuring the development of compensatory adaptive reactions is the increase of capacity of protein-synthesizing apparatus, the activation of biosynthesis of dNTP and DNA against the treatment with damaging factors.