Kinetics of DNA Repair Under Chronic Irradiation at Low and Medium Dose Rates in Repair Proficient and Repair Compromised Normal Fibroblasts

We present time and dose dependencies for the formation of 53BP1 and γH2AX DNA damage repair foci after chronic radiation exposure at dose rates of 140, 250 and 450 mGy/day from 3 to 96 h, in human and mouse repair proficient and ATM or DNA-PK deficient repair compromised cell models. We describe the time/dose-response curves using a mathematical equation which contains a linear component for the induction of DNA damage repair foci after irradiation, and an exponential component for their resolution. We show that under conditions of chronic irradiation at low and medium dose rates, the processes of DNA double-strand breaks (DSBs) induction and repair establish an equilibrium, which in repair proficient cells manifests as a plateau-shaped dose-response where the plateau is reached within the first 24 h postirradiation, and its height is proportionate to the radiation dose rate. In contrast, in repair compromised cells, where the rate of repair may be exceeded by the DSB induction rate, DNA damage accumulates with time of exposure and total absorbed dose. In addition, we discuss the biological meaning of the observed dependencies by presenting the frequency of micronuclei formation under the same irradiation conditions as a marker of radiation-induced genomic instability. We believe that the data and analysis presented here shed light on the kinetics of DNA repair under chronic radiation and are useful for future studies in the low-to-medium dose rate range.

"Subacute" course of chronic radiation syndrome

Introduction. The use of ionizing radiation as a production factor in the late 1940s - early 1950s. began in the absence of a clear understanding of the permissible radiation doses for workers, as well as knowledge of diagnostic criteria and developed therapeutic measures for developing chronic radiation sickness (CRS). Since then, a great deal of experience has been accumulated in the diagnosis and treatment of CRS. Currently, there are no conditions at the workplace for chronic exposure of workers in doses exceeding the permissible ones. However, taking into account the constant expansion of the scope of using sources of ionizing radiation, it is necessary to remember about the possibility of CRS development due to prolonged exposure in case of violation of their storage or their loss. The study aimed to explore the formation of radiation bone marrow syndrome (RBS) due to chronic exposure in doses that exceed the maximum permissible, accumulated with different dose rates of radiation. Material and methods. We selected the medical records of 27 people (24 men and 3 women) who had RBS as a result of chronic professional gamma radiation exposure. The selection criteria were the diagnosis of grade II-III chronic radiation syndrome (CRS) in the presence of agranulocytosis or anemic syndrome in the period of the disease formation and, especially, in the development of myelodysplastic syndrome (MDS) or aplastic anemia in the period of the CRS consequences. Identified clinical and dosimetric CRS features of 27 patients exposed to chronic irradiation with a dose rate of 0.0002-0,009 Gy/h and the summary dose of 1.7 and 9.6 Gy, accumulated over a period of 6 to 96 months were compared the characteristics of 84 patients CRS exposed a lower dose rates (less than 0,0003 Gy/h) and 26 patients with acute radiation syndrome moderate (II) severity as a result of irradiation the dose rates of 0.14-3,7 Gy/h, total dose of 2 to 4 Gy. Results. The criteria of atypical subacute CRS course are identified: the rate of chronic radiation exposure - not less than 0.001-0.009 Gy/h with a summary dose of 1.7-9.6 Gy accumulated over a period of 6-96 months, the presence of agranulocytosis in the period of CRS formation and anemic syndrome in the periods of CRS formation and outcomes. These signs predict the development MDS in 60% of the patients in the period of the CRS consequences. Conclusion. Retrospective study determined that long-term human exposure to a dose rate of 0.001-0,009 Gy/h (0,005-0,05 Gy/day) and more in the accumulation of a summary dose of 1.7 and 9.6 Gy and duration of contact 6-96 months in 60% of cases can be expected development CRS with a subacute clinical course RBS. The main factor determining this feature of the course of RBS is the dose rate exceeding 0.001 Gy / h (2 Gy/year). In the subacute course of CRS, the early outcome in MDS is essentially deterministic. The development of agranulocytosis and anemic syndrome are typical signs of the subacute course of CRS.

Comparing the risk of mortality from solid cancer after radiation incidents and occupational radiation exposure

The purpose of the study is to compare the excess relative risk (ERR per 1 Sv) of solid cancer mortality in acute - catastrophic or emergency, and occupational - fractionated or chronic exposure. Materials and research methods. A maintained database (database of sources) on nuclear workers from about 40 countries, on the basis of it a combined data analysis was carried out to determine the integral ERR value per 1 Gy for cancer mortality for comparison with parameters of cohorts exposed to catastrophic and emergency exposure: the LSS cohort victims of the atomic bombings in Japan, residents of the Techa River (radioactive contamination due to emissions from the Mayak plant) and Russian liquidators of the Chernobyl accident. Results. Comparison of the ERR per 1 Sv for cancer mortality for workers in the global nuclear industry (combining analysis of data from 37 studies) with the parameters of the LSS cohort, residents on the Techa River and liquidators of the Chernobyl accident showed the absence of logical and principial differences, and the risks for the last two cohorts were the highest. Although the data obtained partly confirm the approach of recent years by the United Nations Scientific Committee on the Effects of Atomic Radiation, according to which the carcinogenic effects of acute, accidental, and fractionated or chronic radiation exposure do not depend on the dose rate factor (DDREF), nevertheless, taking into account biological mechanisms and data radiobiological experiments, this issue cannot be considered unambiguously resolved. Conclusion. Based on the ERR per 1 Sv, the average external dose, and the annual background cancer mortality in Russia and the United States, the expected increase in cancer mortality for 100,000 nuclear workers will average 32-69 people over 10 years (0.032-0.069% of the group). Such risks, due to the many carcinogenic non-radiation factors of life and work, as well as fluctuations in the background value, cannot be taken into account in the practice of medicine and health care.

Altered Gut Microbiota Associated With Hemorrhage in Chronic Radiation Proctitis

Pelvic cancer radiotherapy may cause chronic radiation proctitis (CRP) that adversely affects patient’s quality of life, especially in patients with prolonged hematochezia. However, previous studies of radiation enteropathy mainly focused on acute irradiation hazards, and the detailed pathogenesis process and mechanism of prolonged hematochezia associated with radiation-induced toxicity remain unclear. In this study, we characterized the gut microbiota of 32 female CRP patients with or without hematochezia. Differential patterns of dysbiosis were observed. The abundance of Peptostreptococcaceae, Eubacterium, and Allisonella was significantly higher in CRP patients with hematochezia, while the compositions of the Lachnospiraceae, Megasphera, Megamonas, and Ruminococcaceae were lower in the microbiota of non-hematochezia patients. Functional prediction suggested significant difference in the expression of mineral absorption and the arachidonic acid metabolism proteins between hematochezia and non-hematochezia patients, possibly interdependent on radiation-induced inflammation. This study provides new insight into the altered composition and function of gut microbiota in patients with hematochezia, implying the potential use of probiotics and prebiotics for assessment and treatment of CRP.

Thoracodorsal Artery Perforator Flap for Chronic Radiation-Induced Ulcer of the Axilla in Vietnam

Breast cancer is the leading cause of death in females worldwide. Radiotherapy plays an important role for locoregional control in the comprehensive management of breast cancer. Chronic radiation-induced ulcer of the axilla can occur, and it is complicated to treat for these lesions. The application of a thoracodorsal artery perforator flap offers many advantages to be one of the most efficient treatments for radiation-induced ulcers of the axillary region. We introduce a series of 5 patients with radiation-induced ulcers of the axilla treated by using a thoracodorsal artery perforator flap. The mean operative time was 190 minutes. During at least a two-year follow-up, no complication has been found, and the patient has achieved good cosmetic result without movement limitation of the upper limb.

Argon plasma coagulation for the treatment of chronic radiation proctitis – real-world data from Indonesian National Cancer Center

Background: This study aimed to evaluate the endoscopic features and clinical outcome of patients with chronic radiation proctitis (CRP) at one year after argon plasma coagulation (APC) treatment. Method: Between March 2016 and September 2019, a total of 48 female patients with CRP were treated with APC and their medical records were retrospectively reviewed. APC treatment was done every 3 to 54 weeks, with a median of 8 weeks. Number of APC was decided by the treating physician according to the severity of illness. Endoscopic and clinical features at one year after the final APC were recorded as the effectiveness of APC.Results: Of 48 patients, 26 patients were included in this study. Number of APC sessions varied between 1 to 5 sessions of APC for each patient. Of 26 patients, 22 patients achieved clinical improvement and four patients did not achieve clinical improvement at one year after the last APC session. Of the four patients who failed to achieve clinical improvement, two patients underwent surgery, one patient had occasional mild rectal bleeding, and one patient required regular transfusion. Of 22 patients with clinical improvement at one-year after the last APC, improvement of endoscopic features was found in 20 patients. Of four patients who did not achieve endoscopic improvement, diagnostic colonoscopy showed telangiectasis of more than 50% of rectal surface in 1 patient, presence of blood in 2 patients, and presence of ulceration of 1 cm in 1 patient.Conclusion: APC is an effective treatment option for CRP.

Rectal irrigation as rescue therapy for refractory and severe hemorrhagic radiation proctitis: a case report

Hemorrhagic chronic radiation proctitis (CRP) refractory to endoscopic therapy is rare. Because of its high morbidity and mortality rates, proctectomy is considered as the last resort. We report the successful treatment of severe hematochezia refractory to endoscopic therapy and diverting colostomy in a patient with CRP via rectal irrigation.