The influence of redox status on inter-individual variability in the response of human peripheral blood lymphocytes to ionizing radiation.

PURPOSE: Ionizing radiation (IR) can act on atomic structures, producing damage to biomolecules. Earlier investigations evaluating individual radiosensitivity in vitro were focused on cytogenetic biomarkers (chromosomal aberrations - CA and micronuclei - MN). Since IR can also cause oxidative damage by producing reactive oxygen species, the main goal of this investigation was to establish the influence of redox status on CA and MN frequency in human peripheral blood lymphocytes. MATERIALS AND METHODS: Blood samples from 56 healthy donors were irradiated at doses of 0, 0.75, 1.5 and 3 Gy and then analyzed cytogenetically and biochemically. RESULTS: The results showed inter-individual variability in all analyzed parameters, as well as dose-dependent increases in almost all of them. Correlation analysis indicated no association between CA, MN and oxidative stress parameters. However, findings for overall response (HRR) parameters showed that donors with lower values for parameters of antioxidant status had increased levels of cytogenetic damage and higher responses to irradiation and vice versa. CONCLUSION: Besides well-established cytogenetic biomarkers of radiation exposure, our results indicated promising future use for biochemical oxidative status parameters in routine radiation protection practice, since together they can provide a complete radiation response profile in cases of continuous low-dose exposure, as well as in a radiation emergency.

Cytogenetic surveillance of persons occupationally exposed to genotoxic chemicals.

Human genotoxic exposures can occur environmentally, occupationally, or medicinally. The aim of this study was to assess cytogenetic damage (chromosomal aberrations and micronuclei) in persons exposed to chemical agents in medical, agricultural, and industrial occupations. The results showed influences of age, gender, occurrence, and duration of exposure on the extent of cytogenetic damage, but no influence of smoking. Persons exposed to pesticides were allocated significantly higher values of most examined parameters. Among all tested parameters, logistic regression analysis marked tMN, CB, and iCB as the best predictors with high discrimination accuracy of separation between exposed and unexposed persons. The obtained data encourage us to consider certain cytogenetic parameters as valuable markers for preventive medical screening as the extent of cytogenetic damage reflects cumulative exposure events and possible health consequences related to chronic occupational genotoxic exposure.

Micronuclei as a marker for medical screening of subjects continuously occupationally exposed to low doses of ionizing radiation.

CONTEXT: Genotoxicity assays are widely employed in human biomonitoring studies to assess genetic damage inflicted by genotoxic agents. OBJECTIVE: Evaluation of micronuclei (MN) as a screening marker of occupational ionizing radiation (IR) exposure. MATERIALS AND METHODS: Using micronucleus test, peripheral blood lymphocytes (PBL) of 402 control and exposed subjects were screened for genetic damage. RESULTS: The mean frequencies of micronucleus test parameters were significantly higher in exposed persons. Increase of micronucleus yield with duration of exposure (DOE) by 0.303MN/year was revealed. DISCUSSION AND CONCLUSION: The obtained data encourage us to consider MN as valuable markers for preventive medical screening of occupationally exposed groups.

Overweight and obesity in children and adolescents from Serbia in the period 2001-2004 and 2011-2014.

OBJECTIVE: In recent years an increasing prevalence in overweight and obesity of children and adolescents has been recorded worldwide. Childhood obesity is a risk factor for adulthood obesity. The aim of the study is to examine the prevalence of overweight and obesity in children and adolescents aged 7-19 in a 10-year long period in Serbia. SUBJECTS AND METHODS: Cross sectional investigation was conducted in the periods 2001-2004 and 2011-2014. The first investigation included 8965 individuals, 4344 schoolboys and 4621 schoolgirls aged 7-19, while the second investigation included 2507 schoolboys and 3083 schoolgirls. The body mass index (BMI kg m(-2)) was obtained from the recorded height and weight and the assessment of overweight and obesity was based on IOTF reference values. RESULTS: In the first period investigation overweight prevalence was detected in 18% of subjects (21.1% in boys and 15.1% in girls) and obesity prevalence in 5.5% of subjects (6.7% in boys and 4.4% in girls). In the second investigation the overweight and obesity prevalence was observed in 17.4% and 4.5% of subjects, respectively (20.6% in boys and 14.8% in girls; 5.3% in boys and 3.9% in girls). CONCLUSION: The results indicate that in the ten-year period there has been no increase in the number of overweight and obese children and adolescents in Serbia.

A cytogenetic study of hospital workers occupationally exposed to radionuclides in Serbia: premature centromere division as novel biomarker of exposure?

PURPOSE: The health risk of chronic exposure to radionuclides includes changes in the genome (e.g., chromosomal aberrations and micronuclei) that increase chromosomal instability. There are also other phenomena, which seem to appear more frequently in metaphases of exposed persons (such as premature centromere division). The aim of this study was to discover whether or not there is correlation between incidence of named cytogenetic changes in persons occupationally exposed to radionuclides in comparison with unexposed control group, and if significant correlation is determined, can premature centromere division be consider as a biomarker of radiation exposure? METHODS: The exposed group comprised 50 individuals occupationally exposed to radionuclides. The reference control group consisted of 40 unexposed individuals. Chromosomal aberrations, micronuclei and premature centromere division were analyzed according to a standard International Atomic Energy Agency protocol. Statistical analyses were performed using SPSS 17.0 statistics. RESULTS: The means for analyzed cytogenetic changes were significantly higher in the exposed group. Positive correlation between them was found in exposed group. Premature centromere division parameter PCD5-10 was selected as particularly suitable for separating groups (exposed/unexposed). CONCLUSIONS: Identification of other phenomena related to radionuclide exposure, beside well known, may clarify recent problems in radiobiology concerning the biological response to low doses of ionizing radiation and its consequences.

Inter-individual variability in the response of human peripheral blood lymphocytes to ionizing radiation: comparison of the dicentric and micronucleus assays.

Ionizing radiation can induce a wide range of DNA damage that leads to chromosomal aberrations. Some of those aberrations (dicentrics and micronuclei) are applied in biodosimetry. Biological dosimetry assumes similar radiosensitivity of each donor, but it does not exclude inter-individual variations in radiation susceptibility. Therefore, for biological reasons, it is always challenging to investigate inter-individual variability in response to radiation. For mechanistic reasons, it is also interesting to investigate the correlation between dicentric and micronuclei formation in response to radiation. In this experiment, irradiated blood specimens from 14 healthy male and female donors have been used to evaluate inter-individual variability in response to the genotoxic effects of X-ray radiation, as well as the dose-response relationship and test sensitivity using two endpoints (dicentrics and micronuclei). The results showed similar patterns of cytogenetic biomarker distribution between donors, but differences in the response of some donors at some doses. Data also showed that responses of male donors were better detected using the dicentric test, while for females, micronucleus frequencies were higher in response to the same dose of radiation. No influence of smoking status or age on specific responses was observed. Group variability in response to radiation was evaluated using coefficient of variation for each group of individuals irradiated with the same doses; as the dose increases, group variability becomes substantially lower. Despite sporadic inter-individual variability, trend of radiation-induced changes was similar. Produced calibration curves for both types of damage revealed dicentrics as genetic damage more typical for radiation than micronuclei.

Detection of premature segregation of centromeres in persons exposed to ionizing radiation.

We have analyzed the frequency of premature centromeric division (PCD) in medical personnel professionally exposed to low doses of radiation. They had chromosome aberrations (CAs) involving dicentric chromosomes, ring chromosomes, acentric fragments, chromosome breaks, and chromatid breaks. The study included 30 exposed subjects and 23 controls who were each analyzed by a conventional cytogenetics procedure and subsequently by fluorescent in situ hybridization (FISH). The latter was applied particularly in order to verify PCD in a specific chromosome (chromosome 18) in both metaphases and interphase nuclei. The results revealed a significant difference (p < 0.001) in frequencies between the two groups (exposed and controls) for all the observed variables (CAs), metaphases with PCD (MPCD), total number of chromosomes with PCD (TPCD), number of PCD metaphases in acrocentric chromosomes (MAPCD), and the total number of acrocentric chromosomes with PCD (TAPCD). The doses of ionizing radiation absorbed by the subjects' bodies were measured with thermoluminescent dosimeters once a month during the duration of occupational exposure. They were expressed in mSv, as mean annual effective doses for the period of exposure. The Spearman rank test showed a high positive correlation between total life effective dose and frequency of CAs and PCD. Based on the results obtained in this study, we suggest that PCD, as a phenomenon manifesting chromosomal instability (CIN), should be considered as a suitable cytogenetic biomarker for individuals occupationally exposed to ionizing radiation.

Chromosomal aberrations in subjects exposed to ionizing radiation.

Occupational exposure to low doses of ionizing radiation is a particularly delicate subject for investigation, due to the cumulative effects of chronic exposure. It is extremely important to consider and to measure the biological response to given conditions of exposure. The aim of this study was to establish possible recovery from DNA damage in subjects professionally exposed to radiation in their working area by examinations for chromosomal aberrations (CA) at two different times. The first group (I) was composed of 30 professionally exposed subjects in whom unstable CA (dicentrics, ring, acentric fragments, chromatid, chromosomal breaks, and chromatid interchanges) were identified at time zero. After removal from the radiation area, they were re-examined 9 months later. The second group (II) contained 64 healthy individuals, not professionally exposed to ionizing radiation or other known mutagenic agents. In the group of exposed individuals, five (16.67%) subjects exhibited permanent unstable CAs, even after 9 months absence from the radiation. When the nonexposed and exposed groups were compared, an increase of unstable aberrations (p < 0.05) was observed in the exposed group. Nevertheless, a statistically significant decrease of dicentrics, acentric fragments, and ring frequencies was observed in exposed individuals after 9 months away from the radiation area. However, chromatid and isochromatid break frequencies increased slightly but not significantly after 9 months. The detected CAs corresponded to the total effective doses of radiation measured in our subjects. The existence of CAs in some individuals even after absence from the radiation area suggests that the time necessary for the damaged DNA to recover is extremely variable and indicates interindividual differences in radiosensitivity as well as differences in the cellular-reparation response.

Examination of the health status of populations from depleted-uranium-contaminated regions.

During the NATO air strikes on the Federal Republic of Yugoslavia (Serbia and Montenegro) in 1999, depleted-uranium ammunition was used on 112 locations, mainly Kosovo, in the south of Serbia, and one location in Montenegro. Blood samples of residents from depleted-uranium-contaminated areas were gathered and blood cell and chromosomal aberrations were analyzed. During the last 3 years blood samples from 21 residents of Kosovo (Strpce), from 29 residents from the south of Serbia (the Vranje and Bujanovac regions), and from 19 technical television workers from the site of Pljackovica, in the vicinity of Vranje, were collected. Blood samples from 33 residents of central Serbia and 46 occupational workers exposed to X-rays were used as controls. All subjects studied were without any clinical symptoms of disease. The examinations included general clinical assessment; urine samples for alpha-and gamma-spectrometry analysis; complete blood counts; ratio-percentages of blood cells in stained (Giemsa) capillary smears, individual leukocyte line elements; morphological changes observed under a microscope; the presence of immature forms or blasts; and leukocyte enzyme activity [alkaline phosphatase leukocyte (APL)]. Chromosomal aberrations were evaluated in 200 peripheral blood lymphocytes in mitosis. An increased incidence of rogue cells and chromosomal aberrations was found in the blood of the residents of Vranje and Bujanovac, but this was below the incidence of chromosomal aberrations in individuals occupationally exposed to ionizing irradiation. Blast cells were not found. Blood counts were decreased in only a few samples, while morphological changes of both nuclei and cytoplasm were marked in individuals in south and central Serbia. Enzymatic activity (as measured by the APL score) was decreased in samples with chromosomal aberrations and cyto-morphological changes in subjects from the south of Serbia. The contamination level measured by this examination was low. Because of the presence of depleted uranium (uranium-238) in the soil and in plants, the prevention of consequences necessitates the identification of the initial biological effects on sensitive tissues. Early identification of serious blood cell changes is important for appropriate medical treatment.