CYTOGENETIC BIODOSIMETRY OF ACCIDENTAL EXPOSURES IN THE LONG TERMS AFTER IRRADIATION.

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.

ACUTE MYELOID LEUKEMIA, PROSTATE AND SKIN CANCER IN ACUTE RADIATION SYNDROME SURVIVOR AFTER THE 1986 CHERNOBYL NUCLEAR ACCIDENT: CASE REPORT.

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.

[The Problem of the Relationship of the Chromosome Aberration Frequency in Peripheral Blood Lymphocytes with the Risk of Disease Development Including after Irradiation].

This paper presents an analysis of the data published in the scientific literature in connection with the prob- lem of forecasting the risk of development of malignant and non-malignant diseases by chromosome aberra- tion frequencies in cultures of human peripheral- blood lymphocytes. This question is closely linked with the concept of a common chromosomal instability. At the end of the twentieth century evidence of the possibility of such forecast for malignant diseases appeared when cytogenetic indices did not exceed control values on the whole. At the same time there are significant uncertainties due to interindividual and intraindividual variability. In addition, there are significant difficulties concerning distinction of chromosome aberrations induced by environmental influences (for example, radiation) and those due to the possibility of internal processes in the body. For non-malignant diseases the applicability of a similar approach to risk evaluation is not sufficiently substantiated.

[Retrospective Cytogenetic Dose Evaluation. II. Computer Data Processing in Persons Irradiated in Different Radiation Accidents].

The method for retrospective dose assessment based on the analysis of cell distribution by the number of dicentrics and unstable aberrations using a special computer program was earlier developed based on the data about the persons irradiated as a result of the accident at the Chernobyl nuclear power plant. This method was applied for the same purpose for data processing of repeated cytogenetic studies of the patients exposed to γ-, γ-ß- or γ-neutron radiation in various situations. As a whole, this group was followed up in more distant periods (17-50 years) after exposure than Chernobyl patients (up to 25 years). The use for retrospective dose assessment of the multiple regression equations obtained for the Chernobyl cohort showed that the equation, which includes computer recovered estimate of the dose and the time elapsed after irradiation, was generally unsatisfactory (r = 0.069 at p = 0.599). Similar equations with recovered estimate of the dose and frequency of abnormal chromosomes in a distant period or with all three parameters as variables gave better results (r = 0.686 at p = 0.000000001 and r = 0.542 at p = 0.000008, respectively).

Review of the correlation between results of cytogenetic dosimetry from blood lymphocytes and EPR dosimetry from tooth enamel for victims of radiation accidents.

The goal of this study was to compare dose estimates from electron paramagnetic resonance (EPR) dosimetry with teeth and cytogenetic dosimetry with blood lymphocytes for 30 victims of radiation accidents. The whole-body exposures estimated by tooth enamel EPR dosimetry were ranging from 0.01 to 9.3 Gy. Study group comprised victims exposed to acute and prolonged irradiation at high and low dose rate in different accidents. Blood samples were taken from each of them for cytogenetic analysis. Aberrations were scored and analysed according to International Atomic Energy Agency (IAEA) guidelines for conventional and FISH analysis. Tooth samples were collected in dental clinics after they had been extracted during ordinary practice. EPR dosimetry was performed according to the IAEA protocol. EPR dosimetry showed good correlation with dosimetry based on chromosomal analysis. All estimations of cytogenetic dose below detection limit coincide with EPR dose estimates within the ranges of uncertainty. The differences between cytogenetic and EPR assays may occur in a case of previous unaccounted exposure, non-homogeneous irradiation and due to contribution to absorbed dose from neutron irradiation.

A cytogenetic follow-up of some highly irradiated victims of the Chernobyl accident.

A follow-up of 10 highly irradiated men, mostly reactor crew, from the Chernobyl accident is described. Their pre-accident medical conditions and relevant medical status approximately 10-13 y later are listed. A comparison is made between estimates of their average whole-body penetrating radiation doses derived from several biological parameters. First estimates were based on their presenting severity of prodromal sickness, early changes in blood cell counts and dicentric chromosome aberrations in lymphocytes. In three cases ESR measurements on tooth enamel were also made. Retrospective dosimetry using FISH translocations was attempted 10-13 y later. This showed good agreement for those patients with the lower earlier dose estimates, up to about 3 Gy. For the others, extending up to about 12 Gy, the translocations indicated lower values, suggesting that in these cases translocations had somewhat declined. Repeated chromosomal examinations during the follow-up period showed an expected decline in dicentric frequencies. The pattern of decline was bi-phasic with a more rapid first phase, with a half-life of approximately 4 months followed by a slower decline with half-lives around 2-4 y. The rapid phase persisted for a longer time in those patients who had received the highest doses. 10-13 y later dicentric levels were still above normal background, but well below the translocation frequencies.

Cytogenic investigations of serious overexposures to an industrial gamma radiography source.

This paper describes the sequence of events, medical aspects and dose estimations for two radiographers and their driver who were seriously exposed to an iridium-192 industrial radiography source that became detached from its wind-out cable. The men came to medical attention about 1 month later by which time all three were severely leucopenic and one had skin burns on both hands. Doses were estimated by (i) physics calculations combined with their accounts of the event. (ii) the levels of depression of their blood neutrophils, (iii) electron spin resonance on tooth enamel and (iv) blood lymphocyte chromosomal analyses by the conventional dicentric and the fluorescence in situ hybridisation methods. Intercomparison of these methods for estimating doses showed a good level of agreement. In brief, the averaged whole body dose for the most seriously exposed man was about 2.5-3.0 Gy and for the others it was 1.0-2.0 Gy.