Transplantation of mesenchymal stem cells (MSCs), at early and later stages after local exposure of rats to 140 Gy 90Sr/90Y beta radiation, was found to stimulate recovery of damaged skin. The area of local radiation injuries (LRIs) and accelerated healing of radiation ulcers was obtained. Clinical evolution showed the high efficiency of the transplantations of autologous MSCs for the treatment of deep beam ulcers, usually refractive to standard conservative treatment. Analogous to our results in the rats the authors obtained promising results with the application of MSCs for the treatment of severe LRIs in two human patients. Their radiation ulcers showed complete healing after stem cell application. Thus, further developments should determine the best possible conditions for MSC use in LRI treatment.
The long-term in vivo cytogenetic effects of high-dose radiation exposure can be traced in accidentally irradiated persons, and particularly useful for developing strategies of monitoring and therapy of such patients, as well as for elucidating the fundamental aspects of hematopoiesis and radiobiology. Using 24-color fluorescent in situ hybridization (mFISH), we analysed the frequency and the spectrum of chromosomal aberrations (CA) in peripheral blood lymphocytes of the Chernobyl Nuclear Power Plant (NPP) accident victim 30, 31, 32 and 33 years after acute accidental exposure to high-dose gamma radiation of the whole body. Totally, 993 metaphase cells were analyzed (or 219, 272, 258, 244 cells each year), of which 297 were aberrant. Our study demonstrated a constant aberrant cell frequency at 28% in 2016–2018 years, while in 2019, a significant increase up to 35% occurred due to contribution of significantly elevated frequency of simple aberrations in the absence of evident recent genotoxic factors. Four clonal aberrations were detected, three of which persisted for more than one year at a frequency up to 2.5% of analyzed cells. The distribution of 731 breakpoints per individual chromosomes was nearly proportional to their physical length, excepting Chromosomes 13 and 20, which were significantly breakpoint-deficient compared to the genome median rate. Monitoring of the long-term effects on chromosomal instability caused by radiation exposure is important for understanding and predicting the long-term effects of ionizing radiation.
The development of hemoblastosis is often associated with the influence of various genotoxic unfavorable factors, in particular, with the effect of ionizing radiation. This article presents a case report of acute myeloid leukemia (AML) in a patient who was involved in the 1986 accident at the Chernobyl Nuclear Power Plant and suffered an acute radiation syndrome of degree II severity. Based on clinical and cytogenetic dosimetry, the average absorbed radiation dose to the whole body was estimated to be 4.3 Gy. During long-term clinical follow-up (27 years), moderate transient instability of hematological parameters was observed: lymphocytosis, leukopenia and thrombocytopenia, which was associated with chronic viral hepatitis C. Further cytogenetic investigations demonstrated a very high frequency of translocations, up to 50 times background values, that persisted over 3 decades. In 2014, the patient was diagnosed and operated on for prostate cancer and received a course of radiotherapy (total fractionated local dose of 35 Gy) in May 2015. From December 2015 through April 2016, the patient experienced general weakness and developed progressive cytopenia. A diagnosis of AML, resulting from a myelodysplastic syndrome, was confirmed by abnormal complex clones detected in 38% of metaphases by the mFISH-method, along with other chromosomal rearrangements. The patient underwent several chemotherapy treatments for AML but eventually died of bilateral pneumonia in March 2017.
Thirty-five years have passed since the moment of the disaster at the Chernobyl nuclear power plant. It is quite a sufficient period to assess the correctness of the organisation of medical care for victims, to summarise the results of monitoring the health status of various groups of persons involved in the accident, including its direct participants. Radiation from a massive source of relatively uniform gamma radiation and a heterogeneous source of beta radiation can cause affected people to develop acute radiation syndrome (ARS) of varying severity, including non-curable forms of the disease ARS developed in 134 patients; 28 patients from 134 with ARS died in a short time (100 d) after exposure. Among the patients whose disease ended in death, 2/3 of the outcome could be due to radiation skin lesions (19 people). Treatment of ARS varying severity, which was combined with common skin burns with beta radiation, requires long-term specialised treatment. The experience of treating this group of patients has demonstrated that the indications for bone marrow transplantation in the curable form of ARS are limited. The percentage of victims who have absolute indications for allogeneic bone marrow transplantation and in whom this procedure will lead to an improved prognosis for life is very small. Recovery of own myelopoiesis and survival are possible after whole-body irradiation from 6 to 8 Gy, which was found after rejection of haploidentical human leucocyte antigen transplantation, as well as in patients who did not use bone marrow transplantation due to the absence of a corresponding donor. Patients who have undergone ARS need lifelong medical supervision and the provision of necessary medical care.
The group of radiation victims who had received radiation injures similar to those of Chernobyl accident victims was evaluated in terms of retrospective cytogenetic biodosimetry in the long term period of from 17 y up to 50 y after irradiation. Based on the existing results of the long-term cytogenetic examination of the victims injured after the Chernobyl accident, an original method was developed. This method of retrospective dose recovery was based on the use of a special computer program, the time elapsed after irradiation and the frequency of atypical chromosomes. Both patient groups were examined using conventional cytogenetic analysis. The new method of a retrospective biodosimetry was tested on the non-Chernobyl group. As a result the multiple regression equations which included frequency atypical chromosomes produced better results because the majority of the estimates of the retrospective doses fell into the 95%-prediction intervals for the reference group of the Chernobyl victims.
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