Laser-based flow cytometric analysis of genotoxicity of humans exposed to ionizing radiation during the Chernobyl accident

An analytical technique has been developed that allows laser-based flow cytometric measurement of the frequency of red blood cells that have lost allele-specific expression of a cell surface antigen due to genetic toxicity in bone marrow precursor cells. Previous studies demonstrated a correlation of such effects with the exposure of each individual to mutagenic phenomena, such as ionizing radiation, and the effects can persist for the lifetime of each individual. During the emergency response to the nuclear power plant accident at Chernobyl, Ukraine, USSR, a number of people were exposed to whole body doses of ionizing radiation. Some of these individuals were tested with this laser-based assay and found to express a dose-dependent increase in the frequency of variant red blood cells that appears to be a persistent biological effect. All data indicate that this assay might well be used as a biodosimeter to estimate radiation dose and also as an element to be used for estimating the risk of each individual to develop cancer due to radiation exposure. 17 refs., 5 figs

Cytogenetic effects in human as the result of the Chernobyl accident

The Chernobyl accident significantly complicated the ecological situation in Ukraine. The existing environmental pollution, which was already rooted in the background, ensures for the most part that the Ukrainian population comes into contact with one of the most powerful universal mutagens - ionizing radiation. This can cause genetic damage in all living beings, including human. As such, it is essential that the Chernobyl accident victims be medically monitored using cytogenetic monitoring – the study of the frequency and spectrum of chromosome aberrations in human peripheral blood lymphocytes with the help of classical (conventional cytogenetics, G-banding analysis) and new (FISHWCP) research methods

Radioinduced Bystander Effect Revealed in vitro and in vivo In Mixed Human Lymphocytes Culture

The new methodic approach to the investigation of radioinduced bystander effect in somatic human cells with the help of G-banding cytogenetics had been elaborated. The frequency of chromosome aberrations had been studied in proposed by us model system - mixed human peripheral blood lymphocytes culture consisted from cells differed on cytogenetic sex markers (XX, XY) and some morphological chromosome peculiarities. 88 cultures (separate and joint) from 5 couples of donors had been established and 9234 G-banded metaphases had been scored. It had been shown that joint cultivation of intact lymphocytes did not influence upon background frequency of chromosome aberrations in mixed culture. Under joint incubation of X-irradiated in vitro (in doses 250 and 1000 mGy) and intact lymphocytes the dose-dependent interaction between marked cellular population and untargeted cells had been established under both doses mean-group cytogenetic effect in bystander cells (4.31 and 6.13 of chromosome aberrations per 100 metaphases) that cultivated with irradiated ones (6.99 and 21.19 of chromosome aberrations per 100 metaphases) elevated their background level (2.27 per 100 metaphases). In mixed cultures established from unexposed donors and Chernobyl liquidators (with radiation doses in range 1010-2370 mGy ) the frequencies of aberrations in irradiated cells were 5,21±0,89 per 100 metaphases, in bystander cells - 4,05±0,64 per 100 metaphases (under 5,63±0,98 and 1,73±0,65 per 100 metaphases in separate cultures). The difference between spectrum of aberrations in exposed and intact cells had been established both in vitro and in vivo - in targeted cells specific cytogenetic markers of irradiation dominated (unstable and stable chromosome exchanges), as well as in bystander cells simple aberrations (chromatid breaks and terminal chromosome deletions that can be consider as the markers of chromosome instability) mainly induced. All cytogenetic effects mentioned above had been characterized by essential interindividual fluctuations. Data received confirmed as the reality of bystander effect in vitro and in vivo as well as the possibility of the revealing of such effect in proposed by us mixed human peripheral blood lymphocytes model system

Chromosome Sensitivity to Bleomycin in Peripheral Blood Lymphocytes from Unexposed and Irradiated Persons

With the help of modifying "G2-bleomycin sensitivity assay" (treatment of human peripheral blood lymphocytes culture in late post-synthetic phase of mitotic cycle by bleomycin in concentrations 0,05 and 5,00 mcg/ml) the investigation of hidden chromosome instability in 9 unexposed donors as well as in 32 persons with different intensity of radiation exposure (patients recovered from acute radiation sickness - ARS and Chernobyl liquidators) had been fulfilled. The basic criterion of chromosomes sensitivity to bleomycin exposure the total frequency of chromosome aberrations, mainly acentric fragments had been considered. In all examined groups the individual levels of chromosome aberrations under identical mutagenic exposure varied in wide range and didnt depend on their initial values in intact cultures. In control donors the mean-group frequencies of chromosome aberrations were 10.37+0.66 (3.0 - 32.0) and 15.54+0.78 (5,0 - 35,0) per 100 cells, additions to background rate of aberrations were 9,14 and 14,31 per 100 cells under bleomycin exposure in concentrations 0.05 and 5.00 mcg/ml, accordingly. Among control donors three hypersensitive persons had been identified with aberrations rate 35.0, 34.0 and 16.0 per 100 cells that can be considered as genetically caused phenomenon. Similar situation had been determined in 10 liquidators with low radiation exposure - the mean-group frequencies of chromosome aberrations were 11.26+0.63 (2.3 - 34.0) and 15.10+0.79 (3.0 - 34.5) per 100 cells, above-background level of aberrations were 9.14 and 14.31 per 100 cells under bleomycin exposure in concentrations 0.05 and 5.00 mcg/ml, correspondingly. In liquidators group three hypersensitive persons had been identified with aberrations rate 34.5, 20.0 and 19.3 per 100 cells. In 19 ARS patients increased mean-group frequency of aberrations induced by bleomycin in both concentrations had been revealed - 16.80±0.50 (8.7 - 38.2) and 28,04±0,63 (6.0 - 60.0) per 100 cells with addition to background aberrations level 13.47 and 24.71 per 100 cells, accordingly. 13 persons with increased chromosome instability (from 22.2 till 60.0 aberrations per 100 cells) had been found. The data received permit to assume that high radiation doses can modify the inherited human susceptibility to mutagen exposure

Genomic damage in children accidentally exposed to ionizing radiation: a review of the literature

During the last decade, our knowledge of the mechanisms by which children respond to exposures to physical and chemical agents present in the environment, has significantly increased. Results of recent projects and programmes focused on children's health underline a specific vulnerability of children to environmental genotoxicants. Environmental research on children predominantly investigates the health effects of air pollution while effects from radiation exposure deserve more attention. The main sources of knowledge on genome damage of children exposed to radiation are studies performed after the Chernobyl nuclear plant accident in 1986. The present review presents and discusses data collected from papers analyzing genome damage in children environmentally exposed to ionizing radiation. Overall, the evidence from the studies conducted following the Chernobyl accident, nuclear tests, environmental radiation pollution and indoor accidental contamination reveals consistently increased chromosome aberration and micronuclei frequency in exposed than in referent children. Future research in this area should be focused on studies providing information on: (a) effects on children caused by low doses of radiation; (b) effects on children from combined exposure to low doses of radiation and chemical agents from food, water and air; and (c) specific effects from exposure during early childhood (radioisotopes from water, radon in homes). Special consideration should also be given to a possible impact of a radiochemical environment to the development of an adaptive response for genomic damage. Interactive databases should be developed to provide integration of cytogenetic data, childhood cancer registry data and information on environmental contamination. The overall aim is to introduce timely and efficient preventive measures, by means of a better knowledge of the early and delayed health effects in children resulting from radiation exposure