The mechanisms of adaptive response. Estimation of capacity of human blood lymphocytes to radiation adaptive response using different criteria

Blood lymphocytes of 15 healthy donors have been investigated for the ability to decrease their radiosensitivity after treatment with low dose irradiation named radioinduced adaptive response (AR). The unstable chromosome aberrations were used to evaluate the radiosensitivity change after irradiation of cells with low adaptive dose (5 cGy) and subsequent high challenge dose (1.0 Gy) in comparison with the effect of challenge irradiation only. Three indexes were used: the frequency of cells with aberrations in all analyzed cells (A), the number of chromosome aberrations per cell (B) and the number of chromosome aberrations per one aberrant cell (C). It has been discovered that all donors examined can be divided into four groups: 1--individuals which cells did not show AR by all indexes used; 2--individuals which cells showed AR by indexes A and B, but not C; 3--AR was demonstrated by indexes B and C; 4--AR was confirmed by all three indexes. Generally accepted repair model for AR formation explains only the case of donor groups 3 and 4, but can not explain the mechanism leading to the case of group 2. For understanding this mechanism, the distribution of metaphases by the number of chromosome aberrations per cell was analyzes for each donor. It was shown that the part of cells without aberrations in group 2 donors increased significantly after treatment with the adaptive and challenge irradiation in comparison with that after irradiation with challenge dose only. The conclusion is that in this case AR is formed as a result of change in the frequency 0 cell class--population shift. The analogous shift was observed in the distributions of metaphases for all donors of the group 4, but was absent in the group 3 donors. The data obtained suggest that AR of blood lymphocytes might be a result of several processes: activation of submutational genome damage repair; population shifts manifested by the change in the part of undamaged cells; and, possibly, activation of apoptotic cell death. The complex nature of AR affects each of radiosensitivity evaluation criteria to a different extent.     

Molecular and cellular mechanisms of the adaptive response in eukaryotes

The mechanisms of adaptive response (AR) which consisted of the increasing of cell and organism resistance to large doses of genotoxic and toxic agents formed after the preliminary influencing of its agents in small doses were discussed. The examples of factors leading to AR (irradiation, radiomimetics, alkylators, H2O2, and hyperthermy) as well as the conditions of its manifestation (in vivo and in vitro, acute and chronic adapting influences) were produced. The AR mechanisms bases on the molecular and cellular levels are the stimulation of protecting system (the synthesis of protecting proteins and antioxidant system activation), the intensification of DNA repair, effect on neurohumoral signal messengers and changes of proliferative activity. On organism level the nonspecific stress-reaction components were added (AKTG and steroid hormones synthesis). It was concluded that no there was no single mechanism of AR to all type of damaging agents. Evidently of that causes of its phenomenon have the complex character. The relatively narrow limits of AR (variability for the cells of different individuals, slight AR in children's cells and full absence of embryo cells) require careful use an AR conformities as the indicator for the professional and referring works.     

Adrenergic mechanisms in the hepatic microcirculation in the rat

The in vivo hepatic microvascular bed of the rat was observed microscopically in the transilluminated liver and the diameter of the hepatic sinusoids was measured by serial photomicrography. Intraportal infusion of tyramine induced concentration-dependent constriction of the hepatic sinusoids, but also dilatation of the sinusoids when the dose was small. These effects were attributed to the release of endogenous noradrenaline which activated either alpha- or beta-adrenergic receptors and caused constriction, or dilatation, of the sinusoids respectively. Adrenaline and noradrenaline induced similar changes in the hepatic sinusoids as tyramine, while phenoxybenzamine induced dilatation, and propranolol constriction, of the sinusoids. All the above responses were abolished by pretreatment with reserpine. A possible noradrenaline-mediated basal vasomotor tone in the hepatic sinusoids for autonomic control of the blood flow in the sinusoids was postulated.     

The phenomenon of adaptive response in radiobiology]

Consideration is given to various adaptive reactions to low-level radiation, their association with an absorbed dose, dose rate, radiation quality and time-interval between exposures, as well as with a cell cycle phase. Possible mechanisms of the adaptive response and the character and role of DNA damages, that can induce gene expression of the adaptive response, are discussed. The data on the influence of a preliminary long-term exposure to low-level radiation on the radiosensitivity of biological objects are analyzed with due regard for the adaptive cell response. It is concluded that the adaptive response of cells to ionizing radiation is a particular case of the phenomenon of cell adaptation to the effect of genotoxic factors of the environment.     

The mechanisms of the action of fluorine on periodontal tissues]

It is stated that fluoride intoxication promotes a sharp intensification of the peroxidation processes in the parodontium tissues. It is caused by a respirator explosion of neutrophils, a decrease in activity of antioxidant system enzymes, thus leading to disturbances of microcirculation and blood coagulation, ischemia development. The last factor can retard the enzymatic oxidation in a cell due to hypoxia, injures lysosomal membranes promoting partial autolysis of parodontium tissues, cell structures, intercellular substance. The interaction of blood with destructive elements of cells and collagen favours the development of trombohemorrhagic reactions in the parodontium tissues. A generalized damage of parodontium arises which intensifies under the effect of any other pathogenetic factors.     

Radioadaptation for gene mutation and the possible molecular mechanisms of the adaptive response

This paper reviews the experimental results showing that a prior exposure to a low dose of ionsing radiation induces an adaptive response expressed as a reduction of gene mutation in various cell systems. The data show that the mutagenic adaptation shares common features with the clastogenic adaptation, i.e., priming dose level, kinds of conditioning agents, time interval between conditioning and challenging treatments, degree of induced protective effect (40–75%), transitory response and inhibition by 3-aminobenzamide, a DNA repair inhibitor. Moreover, the deletion-type mutations are predominantly reduced in adapted cells, suggesting that the mechanism underlying mutagenic adaptation preferentially facilitates the removal of the DNA lesions leading to deletion-type mutations. These lesions are thought to be double-strand breaks which are likely to be also involved in the production of chromosomal damage. Recent findings on the molecular processes implicated in the cellular response to rediation provide some clues for the mechanisms that could be triggered by low-dose exposure and ultimately contribute to the protective effect. These is some evidence that the protein kinase C-mediated signalling pathway is a key step for the transduction of the low-dose-induced signal. Several recent reports indicate that the low-dose triggers changes in the expression of several genes whose products, though most of them are still not identified, would be related to DNA repair and/or control of cell cycle progression.     

Adrenergic mechanisms in control of plasma lipid concentrations.

The mechanisms of the changes in plasma lipids concentrations observed after beta-blockade were examined in 53 patients with hypertension receiving treatment with atenolol, metoprolol, propranolol, and oxprenolol in a randomised cross-over trial. Significant increases in mean plasma total and very-low-density lipoprotein (VLDL) triglyceride and reductions in high-density lipoprotein (HDL) cholesterol and free fatty acids concentrations wer observed with all four drugs, the increase in plasma triglyceride concentration being greatest after propranolol and oxprenolol. No significant changes were observed in total of LDL cholesterol concentrations, but HDL:LDL ratios and HDL cholesterol as a proportion of total cholesterol fell significantly. Thus plasma lipid concentrations should be monitored after three to six months of long-term treatment. Changes in triglyceride, HDL cholesterol and free fatty acid concentrations were associated with a highly significant reduction in clearance of soya oil (Intralipid) in 25 patients studied but were unrelated to changes in blood pressure. The fall in HDL cholesterol and rise in free fatty acid concentrations were significantly less in those with initially reduced HDL cholesterol or raised free fatty acid concentrations respectively. It is proposed that unopposed alpha stimulation inhibits lipoprotein lipase with a subsequent rise in plasma triglyceride and fall in HDL cholesterol concentration. Analysis of the relation between pretreatment concentrations and subsequent changes suggests that excessive alpha stimulation may impair production of HDL cholesterol in those with low HDL cholesterol concentrations before treatment. Subtle catecholamine-mediated changes in plasma lipid concentrations might provide a mechanism for the relation between stress and the development of cardiovascular events.     

Rosette formation and humoral immune response to 2,4-dinitrophenol in mice of different inbred strains]

A study was made of the content of rosette-forming cells to DNP-ovalbumin in the spleen of mice of different inbred strains. The values of the rosette-forming cells and of the titre of serum agglutinins to the DNP-group in DNP--bovine gamma-globulin immunization of mice of these strains were determined. It was shown that there were interstrain differences in respect to the normal and immune rosette-forming cells and also humoral antibodies. There was noted a direct correlation between the number of the immune rosette-forming cells and the antibody titre in the serum of mice of the same inbred strain. Immune response (both by the content of rosettes in the spleen and by the antibody level) proved to be the minimal in mice with the highest level of rosette-forming cells. There proved to be no inverse relationship.     

Adrenergic mechanisms regulating the motor reactions of rats in the early postnatal period

In 12-day-old rats, L-DOPA, a precursor of catecholamine synthesis, provokes an increase in the rate of the motor reactions (MR) of the shudder type. Reserpine which promotes catecholamine release from the tissues, leads to the diminution of the rate of the MR of the shudder type in rats of the same age. Aminazine, an alpha-adrenoblocker and antagonist of dopamine receptors, decreases the rate of the MR of the shudder type. Administration of aminazine in a dose of 10 mg/kg at different age periods produces inconclusive changes in the diminution of the rate of the MR of the shudder type. During sudden changes in the growth, the rate of the above-described modulations substantially decreases. The high rate of the MR of the shudder type seen in rats in the early postnatal period is a consequence of the marked activity of the catecholaminergic (dopaminergic) systems during that period. Reduction in the effect of the decreased MR rate produced by the same dose of aminazine during the critical periods of the growth also attests to the high activity of the catecholaminergic (dopaminergic) system in rats at that period.     

Neurophysiologic mechanisms of the formation of the signal significance of words in yound children]

It has been established by means of the auto- and cross-correlation EEG analysis of children in the second year of life that different functional systems of relationships of cortical structures are formed during the word perception depending on whether it is an indifferent or signal stimulus for the child. In response to indifferent words, synphasic oscillations of the biopotentials appear in the infero-parietal and temporal, as well as in the temporal and frontal zones of the dominant hemisphere, without enhancement of the periodic processes and without appearance of a common rhythm. Signal verbal stimuli produce enhanced highly synchronous, synphasic interconnections of the infero-parietal biopotentials not only with temporal, but more considerably so with the frontal activity of the left hemisphere. This is accompanied by increased periodicity of processes between them and the appearance of a predominant rhythm 4--5 osc/sec.     

Primary response mechanisms of the adrenal cortex in dogs to pain stress]

The adrenal cortex of dogs shows a drop in the glucocorticoid content 10--15 sec after the pain action in the presence of the free cholesterol level increase and its esterified form drop. The concentrations of hormones in the blood falls chiefly at the expense of protein bound hydrocortisone. The subsequent phase of the reaction (after 30--60 sec) is characterized by a considerable accumulation of the hormones by the gland. The level of free glucocorticoids significantly increases, the initial ratio of hydrocortisone and cortisone restores, and transcortin depot is filled up. The role of the adrenal and transcortine depot in realization of feedback mechanisms under stress is discussed.