[A new approach to enhancing the effects of postradiation recovery in various animal species].
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Biomedical subjects
Publications and source records attributed to L M Rozhdestvenskiĭ.
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On the mitotic index curve of the cellular population following radiation there is a linear part. The time interval between the initial decrease of the mitotic index and the extrapolation of the straight part of the curve to X-axes is the mean duration of mitosis. The values of this parameter for the culture of fibroblasts obtained by this method are practically identical with those obtained by a method based on determination of the mitotic index and the doubling time of the cell count.
The time-course of the metronidazole (MZ) radiosensitizing effect after the administration of the agent to mice 7 days following the inoculation of ascites tumor cells is better correlated with the time-course of the MZ content in the above cells than with the time-course of their potential respiration intensity evaluated by the polarographic method in a closed unit. Five minutes after MZ administration the depression of respiration intensity reached 50% and might contribute to the radiosensitizing effect. After MZ administration not only "metronidazole" but also "oxygen" waves were recorded in ascites tumors of mice using the polarographic method.
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There have been analysed the data as own as taken from the literature concerning the action of low level radiation (LLR) on different structure level in a mammalian organism. There have been compared the types of various structures early reactions regarding an acute or prolonged exposure depending on the test type and the studied structure organization level. The data analysis has shown it should differentiate the damaging and irritating action of LLR. The former reveals the radiosensitivity and the latter does the radioreactivity of the structure studied. The damaging radiation action has an threshold and the latter increases in the way from molecular to whole body level. It is supposed the irritating LLR action is realized through the involvement of organism and cell regulative systems. The existence of a threshold in the case is unknown so far.
According to the analysis of epidemiological and experimental data there are evidences in threshold on criterion of mutagenic (in broad sense) ionising radiation action. A threshold takes place in the region of about 20-200 mGy concerning a dose in case of an acute exposure and in the region of the third order above a background level regarding a dose rate in case of chronic or prolonged exposure. Evidences in favour of linear non-threshold conception are based on primitive mathematical extrapolations and approximations of the study results, mainly, in the region of intermediate doses/dose rates. Besides real data in region of low doses are ignored. The latter has a reason in paradigm of stochastic damage action of ionising radiation and in underestimation of cell and organism protection-reparation systems action. Regarding axiomatic bases of ionising radiation action it is possible to conclude more reliable substantiation of the dual (positive-negative) nature and the threshold conception concerning ionising radiation action in comparison with the non-threshold one.
The influence of betaleukin (human recombinant interleukin-1 beta) on the processes of postirradiation recovery of haemopoietic precursors (GM-CFC) and the level of granulocyte-macrophag colony-stimulating factor (GM-CSF) were studied in long-term bone marrow cultures after gamma-irradiation with a dose 2 Gy. Then the betaleukin action on the contents of GM-CFC and induction of GM-CSF in the non irradiated cultures was studied. It was shown that betaleukin increased the induction of GM-CSF and raised the contents of GM-CFC in long-term bone marrow cultures, and the maximal increase of a GM-CSF level and GM-CFC amount was marked in 20 hours after introduction. At an irradiation of long-term bone marrow cultures in conditions of betaleukin introduction 20 hours prior to influence of radiation the smaller degree of damage and faster recovery of GM-CFC was observed. The data in this report suggest that one of the mechanisms of antiirradiation action of betaleukin apparently is connected to the action of the preparation on hematopoietic microenvironment cellular elements, that causes the release of a colony-stimulating factor and stimulation of recovery of haemopoietic precursors.
In experiments on mice F1(CBA x C57BL/6) the dependence of 30th days survival on the time of betaleukin (medicine form of interleukin-1 beta) administering after exposure to 7.5 Gy whole body gamma-irradiation from 137Cs (approximately DL80/30) was studied. Betaleukin was injected subcutaneously in dose 25 mcg/kg 0.2, 1, 3, 6 and 24 h after the exposure. The highest therapeutic effect took place in case of 0.2 h interval, then it dropped but was slightly expressed at 1 h. The hemopoiesis condition was studied in 7 or 9 days after the mice exposure to 6 Gy and betaleukin administering 1 h later in dose 25 or 50 mcg/kg. The positive effect on granulopoiesis beginning from the level of CFU-GM was observed. There were analyzed the reasons of weaker betaleukin effect and shorter period of its effectiveness after exposure in comparison with literature data regarding IL-1.
The analysis of the epidemiological data regarding cancer mortality in cohorts of Japanese A-bomb survivors and Chermobyl liquidators exposed to different doses suggests that there are good reasons for recognizing the threshold of the radiocarcinogenic effect in the region of about 200 Gy (mSv). The analysis of solid cancer mortality in Japanese cohort, which exceeded the expected one in a dose diapason of 5-200 mSv, revealed a (quasi) plateau in a dose-effect curve and led to the conclusion that the nature of the overshoot is non-radiogenic. The analysis of supposedly dose dependent leucosis incidence in the limited low dose diapason in the Chernobyl cohort showed that the real coefficient of the excess absolute or relative radiation risk could not be received in the case because the larger part curve was placed under the control level. In supporting the principle of single hit in a cell nucleus as a base of microdosimetric determination of low radiation doses, the approach to objective delimitation between low, intermediate and high doses regions has been proposed. The low doses upper limit of sparse ionizing radiation for cell nucleus of 8 microns in diameter has been evaluated as 0.65 mGy. It can serve for evaluation of the dose rate threshold regarding the safe chronic radiation levels in the environment.
In experiments with F1 (CBA X C57Bl) mice irradiated with doses of 6.5 to 8.5 Gy the evidence was obtained for the important role of the reimplanted cells in a complete realization of the reparative effect of exfusion, incubation and reimplantation of bone marrow. The increase in radiation dose was accompanied by a tendency towards the decrease in the efficacy of the procedure, and, perhaps, by changes in the ratio of roots of haemopoietic stem cell differentiation.
The ATP content of rat brain was shown to decrease considerably (20-60%) during the first minutes following high-energy electron irradiation with doses of 300 and 500 Gy. A transient nature of changes and a more pronounced decrease in ATP with increasing radiation dose and manifest neurologic disturbances indicate that the energy metabolism is involved in the pathogenesis of early neurologic disturbances in animals.
The polarographic study of the functional status (FS) of rat liver mitochondria subjected to the effect of mexamine in vivo and in vitro and the hypoxic hypoxia in vivo has revealed various FS changes displaying disconnecting and rotenone-like effects and posthypoxic activation. With a mexamine dose of 50 mg/kg in vivo the direct effect of the protector contributes considerably to the mitochondrial FS. Within a wide range of mexamine doses no relationship was found between the pattern of the mitochondrial FS change in the liver and the protective effect with respect to bone marrow.
In experiments with mice, rats, guinea pigs, and dogs subjected to whole-body irradiation a favourable effect of postirradiation explantation, incubation, under suboptimal conditions, and reimplantation of bone marrow cells was shown. The effect was perhaps associated with the enhanced recovery of stem cells, their primary differentiation into a granulocytic series, and activation of bone marrow regeneration.
In experiments with rats, it was shown that whole-body irradiation of animals with a dose of 500 Gy causes a decrease in the catecholamine mediator content of the truncus cerebri during the first minutes following irradiation. A possible mechanism of the changes observed is discussed.
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Incubation, in various conditions, of bone-marrow samples taken from irradiated (7 Gy) (CBA X C57Bl)F1 mice and the subsequent testing thereof for stem potency in the exposed (8.5 Gy) recipients have demonstrated, with certain admissions, that stem cells can recover from radiation injury in certain experimental conditions.