Evaluation of Genetic Damage in Persons Occupationally Exposed to Antineoplastic Drugs in Serbian Hospitals.

INTRODUCTION: Although useful in the treatment of malignant cells, antineoplastic drugs (ANPDs) as chemical genotoxic agents, can interfere with normal cell physiology causing genetic damage and unfavourable health effects, especially in occupationally exposed persons. The Cytokinesis-block Micronucleus (CBMN) Cytome assay has been widely used in human biomonitoring studies as a reliable biomarker of chemical genotoxic exposure. OBJECTIVES: Our comprehensive research was conducted in order to evaluate micronuclei as a marker for preventive medical screening purposes for persons occupationally exposed to ANPDs. METHODS: Using the CBMN Cytome test, peripheral blood lymphocytes of 201 control and 222 exposed subjects were screened for genetic damage. RESULTS: Age and gender influenced micronucleus (MN) frequency, but smoking habit did not. The mean micronuclei frequencies and other parameters of the CBMN Cytome test [numbers of binuclear lymphocytes with one (MN1) or two (MN2) micronuclei] were significantly higher in the group of exposed persons. Positive correlation between duration of occupational exposure and MN frequency was revealed. CONCLUSIONS: The results of our study performed on a large sample confirmed the capacity of the CBMN Cytome assay to serve as a reliable biomarker of long-term ANPD exposure.

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.

New models for prediction of micronuclei formation in nuclear medicine department workers.

BACKGROUND: Ionizing radiation causes detrimental health effects such as cancer and genetic damage. The study aim was to determine predictors for micronuclei (MN) occurrence and frequency in peripheral blood lymphocytes of health workers professionally exposed to radiation. METHODS: Health workers, age matched, selected for the study on regular check-ups, were divided according to the radiation exposure. The exposed group involved nuclear medicine department employees (54) and the control group comprised workers from other departments (36). Data about workers characteristics and habits, received annual doses (AD), total years of service (TYS) and exposed years of service (EYS) were taken from each subject. Blood samples were taken and micronuclei (MN) number in peripheral blood lymphocytes was calculated using CBMN assay according to standard protocols. RESULTS: Most workers were female, technicians, with mean age of 45.67 years and EYS about 15 years. Health workers exposed to radiation had significantly more MN than controls (p = 0.001). Female gender, older age, higher received annual doses, longer EYS and TYS increased the MN number. Technicians and laboratory workers have higher risk for MN occurrence. Significant predictors of MN formation according to constructed model were workers age, sex, AD and EYS. One EYS year increases MN frequency 1.017 times, while receiving 0.1 mSy raises MN frequency by 26 %. EYS accurately predicts 86.30 % of MN frequencies and AD 64.60 %. CONCLUSIONS: The model, developed for the first time in this study, showed that received annual doses and duration of exposure to radiation can be used for prediction of MN numbers.

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.