Dubravka Jovicic

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.

Occupational Exposure in Nuclear Medicine

Occupational exposure to ionizing radiation (IR) involves operations with unsealed or sealed sources. In radiation protection, many biological and physical dosimetry techniques have been established to estimate personal or organ dose equivalent and the effective dose. Nuclear medicine workers operating unsealed sources are of particular interest for bioand physical dosimetry research because of exposure to extremely inhomogeneous fields of ionizing radiation and an increased risk of internal contamination. In addition to external exposure, personnel who work with unsealed radiation sources may also be exposed to radioactive material taken into the body, as it may accumulate in specific organs and emit radiation that is absorbed by the surrounding body tissues. Internal doses received by the organs or whole body can be significant for even small intakes of radioactive material.(1) Internal incorporation of radionuclides constitutes a particular type of protracted irradiation with the added complication that exposure to the human body is usually difficult to quantify. This is because the sites of deposition of a radionuclide and its retention time depend on a large number of factors. These include the physicochemical form, the quality of emitted radiation, the metabolic pathways into which the nuclide may be incorporated, and the subject’s physiological status. Radionuclides can distribute uniformly or non-uniformly throughout the human organism. Only a few radionuclides (137Cs and 3H) distribute homogeneously throughout the human body, while others have uneven distribution. Uneven distribution may include accumulation in critical organs and is dependent on their metabolism.(2–5) In physical dosimetry, whole or partial body counters, or measurement of activity in biological samples such as urine, feces, and so on, are methods of choice for estimation of internal contamination dose.(2–5) Other methods of screening radionuclide intake include monitoring nose blows and nasal swabs, measuring breath for volatile liquids or materials metabolized to gases, and assaying blood serum and other fluids such as sweat (tritium excretion). These techniques are generally only qualitative and their use for dose assessment yields uncertain results.(1) The Serbian Institute of Occupational Health (SIOH) maintains laboratories that are equipped for external dose assessment of personnel exposed to IR. In its cytogenetics laboratory, chromosomal aberration (CA) assay (dicentric test) and cytokinesis block micronucleus (CBMN) tests are performed. The laboratory for personal dosimetry prepares and processes personal dosimeters by the thermoluminescent dosimetry method. Fifty personal dosimeters of workers in the Nuclear Medicine Department (NMD) were processed in December 2007, when unusual values for two technicians were discovered. Those technicians, who were operating unsealed sources in the NMD, were subsequently examined in the cytogenetics laboratory. The results reported here

Micronuclei As A Marker For Medical Screening Of Subjects Continuously Occupationally Exposed To Low Doses Of Ionizing Radiation

Abstract 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.

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

AbstractPurpose 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?MethodsThe 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.ResultsThe 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.

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

Abstract 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

ABSTRACT 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.

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

SUMMARY 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.