Low-dose Ionizing Radiation Exposure Research Articles

AN ImageJ-BASED ALGORITHM FOR A SEMI-AUTOMATED METHOD FOR MICROSCOPIC IMAGE ENHANCEMENT AND DNA REPAIR FOCI COUNTING

Proper evaluation of the health risks of low-dose ionizing radiation exposure heavily relies on the ability to accurately measure very low levels of DNA damage in cells. One of the most sensitive methods for measuring DNA damage levels is the quantification of DNA repair foci that consist of macromolecular aggregates of DNA repair proteins, such as γH2AX and 53BP1, forming around individual DNA double-strand breaks. They can be quantified using immunofluorescence microscopy and are widely used as markers of DNA double-strand breaks. However this quantification, if performed manually, may be very tedious and prone to inter-individual bias. Low-dose radiation studies are especially sensitive to this potential bias due to a very low magnitude of the effects anticipated. Therefore, we designed and validated an algorithm for the semi-automated processing of microscopic images and quantification of DNA repair foci. The algorithm uses ImageJ, a freely available image analysis software that is customizable to individual cellular properties or experimental conditions. We validated the algorithm using immunolabeled 53BP1 and γH2AX in normal human fibroblast AG01522 cells under both normal and irradiated conditions. This method is easy to learn, can be used by nontrained personnel, and can help avoiding discrepancies in inter-laboratory comparison studies examining the effects of low-dose radiation.

Genetic Background Modulates lncRNA-Coordinated Tissue Response to Low Dose Ionizing Radiation.

Long noncoding RNAs (lncRNAs) are emerging as key regulators of diverse cell functions and processes. However, the relevance of lncRNAs in the cell and tissue response to ionizing radiation has not yet been characterized. Here we used microarray profiling to determine lncRNA and mRNA expression in mammary glands of BALB/c and SPRET/EiJ mice after low-dose ionizing radiation (LDIR) exposure. We found that unirradiated mammary tissues of these strains differed significantly in baseline expressions of 290 lncRNAs. LDIR exposure (10 cGy) induced a significant change in the expression of many lncRNAs. The vast majority of lncRNAs identified to be differentially expressed after LDIR in either BALB/c or SPRET/EiJ had a significantly correlated expression pattern with at least one LDIR responsive mRNA. Functional analysis revealed that the response to LDIR in BALB/c mice is highly dynamic with enrichment for genes involved in tissue injury, inflammatory responses, and mammary gland development at 2, 4, and 8 weeks after LDIR, respectively. Our study demonstrates that genetic background strongly influences the expression of lncRNAs and their response to radiation and that lncRNAs may coordinate the tissue response to LDIR exposure via regulation of coding mRNAs.

F1 hybrids of BALB/c and C57BL/6 mouse strains respond differently to low-dose ionizing radiation exposure.

There are evidences to show that response to ionizing radiations have genetic influence. To investigate this further, reciprocal F1 hybrids were generated by crossbreeding the radiation-susceptible BALB/c mouse strain with resistant C57BL/6 in a sex-specific manner (BALB/c♂ x C57BL/6♀ = B6BcF1; C57BL/6♂ x BALB/c♂ =BcB6F1). These hybrids were compared with each other and to the parental strains with respect to transcriptional responses to low-dose ionizing radiation exposure (LDIR). The two F1 hybrids showed drastic differences in their gene expression profiles to ionizing radiation exposure particularly in case of the genes involved in DNA damage response and repair process. Also, the inheritance pattern of the gene expression was found to be complex and could not be explained solely on the basis of parental expression pattern. It was concluded that there is a differential transmission of susceptible trait alleles from the parents to F1 progeny which is dependent on the sex of the parent mouse strain used to set up the crosses and other environmental factors.

An interferon signature identified by RNA-sequencing of mammary tissues varies across the estrous cycle and is predictive of metastasis-free survival

The concept that a breast cancer patient's menstrual stage at the time of tumor surgery influences risk of metastases remains controversial. The scarcity of comprehensive molecular studies of menstrual stage-dependent fluctuations in the breast provides little insight in this observation. To gain a deeper understanding of the biological changes in mammary tissue and blood during the menstrual cycle and to determine the influence of environmental exposures, such as low-dose ionizing radiation (LDIR), we used the mouse to characterize estrous-cycle variations in mammary gene transcripts by RNA-sequencing, peripheral white blood cell (WBC) counts and plasma cytokine levels. We identified an estrous-variable and hormone-dependent gene cluster enriched for Type-1 interferon genes. Cox regression identified a 117-gene signature of interferon-associated genes, which correlated with lower frequencies of metastasis in breast cancer patients. LDIR (10cGy) exposure had no detectable effect on mammary transcripts. However, peripheral WBC counts varied across the estrous cycle and LDIR exposure reduced lymphocyte counts and cytokine levels in tumor-susceptible mice. Our finding of variations in mammary Type-1 interferon and immune functions across the estrous cycle provides a mechanism by which timing of breast tumor surgery during the menstrual cycle may have clinical relevance to a patient's risk for distant metastases.

To know how to be protected: the risks of low-dose ionizing radiation exposure

To know how to be protected: the risks of low-dose ionizing radiation exposure

Comparison of Cancer Risk Associated With Low-Dose Ionizing Radiation from Cardiac Imaging and Therapeutic Procedures After Acute Myocardial Infarction in Women Versus Men

Patients with cardiovascular disease are increasingly exposed to low-dose ionizing radiation (LDIR) from diagnostic and therapeutic procedures. Previous studies have suggested that the malignancy risk associated with LDIR may be greatest in women and in young patients. We sought to compare the effect of LDIR on incident cancer across gender and age strata in a population-based cohort of patients with myocardial infarction (MI). All initially cancer-free patients with MI from 1996 to 2006 were identified in a province-wide administrative database. Procedure-specific LDIR dose estimates were used to generate a cumulative cardiac LDIR exposure variable. Time-dependent multivariate Cox regression was used to determine the relation between cardiac LDIR and incident cancer. A time-lag covariate of 3 years was used wherein a de novo cancer could only be attributed to LDIR incurred at least 3 years earlier. The effect of age and gender on LDIR-associated risk of cancer was evaluated with stratified models and the addition of interaction terms. The study cohort consisted of 56,606 men and 26,255 women. For each millisievert of cardiac LDIR, women were more likely to develop a cancer (hazard ratio 1.005, 95% confidence interval 1.002 to 1.008) than men (hazard ratio 1.002, 95% confidence interval 1.001 to 1.004) after adjusting for age, noncardiac LDIR, and covariates (p for interaction = 0.014). Contrarily, over the range studied (predominantly patients aged >50 years), age was not a determinant of LDIR-associated risk of cancer. In conclusion, women exposed to LDIR from cardiac imaging and therapeutic procedures after MI are at a greater risk of incident cancer compared with men after similar exposure. The extrapolated absolute risk from LDIR exposure would nonetheless be expected to be low.

Radioadaptive Response Following In Utero Low-Dose Irradiation

Acute radiation exposure is known to cause biological damage that leads to severe health effects. However, the effects and subsequent health implications of exposure to low doses of ionizing radiation are unclear. The purpose of this study was to investigate the effects of low-dose ionizing radiation exposures in utero. Pregnant laboratory mice (BALB/c) were exposed to low-dose Chernobyl radiation [10-13 mSv per day for 10 days] during organogenesis. The progeny were born and weaned in an uncontaminated laboratory, then were exposed to an acute radiation dose (2.4 Sv). Analysis of our end points (litter dynamics, DNA damage, bone marrow stem cell function, white blood cell counts and gene expression) suggests that a low-dose (100-130 mSv) in utero exposure to ionizing radiation is not deleterious to the offspring. Rather DNA damage, white blood cell levels, and gene expression results suggest a radioadaptive response was elicited for the in utero exposure with respect to the effects of the subsequent acute radiation exposure.

Adaptive radiation‐induced epigenetic alterations mitigated by antioxidants

Humans are exposed to low-dose ionizing radiation (LDIR) from a number of environmental and medical sources. In addition to inducing genetic mutations, there is concern that LDIR may also alter the epigenome. Such heritable effects early in life can either be positively adaptive or result in the enhanced formation of diseases, including cancer, diabetes, and obesity. Herein, we show that LDIR significantly increased DNA methylation at the viable yellow agouti (A(vy)) locus in a sex-specific manner (P=0.004). Average DNA methylation was significantly increased in male offspring exposed to doses between 0.7 and 7.6 cGy, with maximum effects at 1.4 and 3.0 cGy (P<0.01). Offspring coat color was concomitantly shifted toward pseudoagouti (P<0.01). Maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring. Thus, LDIR exposure during gestation elicits epigenetic alterations that lead to positive adaptive phenotypic changes that are negated with antioxidants, indicating they are mediated in part by oxidative stress. These findings provide evidence that in the isogenic A(vy) mouse model, epigenetic alterations resulting from LDIR play a role in radiation hormesis, bringing into question the assumption that every dose of radiation is harmful.

Low-Dose Ionizing Radiation-Induced Blood Plasma Metabolic Response in a Diverse Genetic Mouse Population

Understanding the biological effects and biochemical mechanisms of low-dose ionizing radiation (LDIR) is important for setting exposure limits for the safe use of nuclear power and medical diagnostic procedures. Although several studies have highlighted the effects of ionizing radiation on metabolism, most studies have focused on uniform genetic mouse populations. Here, we report the metabolic response to LDIR (10 cGy X ray) on a genetically diverse mouse population (142 mice) generated from a cross of radiation-sensitive (BALB/c) and radiation-resistant (SPRET/EiJ) parental strains. GC-TOF profiling of plasma metabolites was used to compare exposed vs. sham animals. From this, 16 metabolites were significantly altered in the LDIR treated vs. sham group. Use of two significantly altered metabolites, thymine and 2-monostearin, was found to effectively segregate the two treatments. Multivariate statistical analysis was used to identify genetic polymorphisms correlated with metabolite abundance (e.g., amino acids, fatty acids, nucleotides and TCA cycle intermediates). Genetic analysis of metabolic phenotypes showed suggestive linkages for fatty acid and amino acid metabolism. However, metabolite abundance was found to be a function of low-dose ionizing radiation exposure, and not of the underlying genetic variation.

Ionizing radiation biomarkers for potential use in epidemiological studies

Ionizing radiation is a known human carcinogen that can induce a variety of biological effects depending on the physical nature, duration, doses and dose-rates of exposure. However, the magnitude of health risks at low doses and dose-rates (below 100mSv and/or 0.1mSvmin(-1)) remains controversial due to a lack of direct human evidence. It is anticipated that significant insights will emerge from the integration of epidemiological and biological research, made possible by molecular epidemiology studies incorporating biomarkers and bioassays. A number of these have been used to investigate exposure, effects and susceptibility to ionizing radiation, albeit often at higher doses and dose rates, with each reflecting time-limited cellular or physiological alterations. This review summarises the multidisciplinary work undertaken in the framework of the European project DoReMi (Low Dose Research towards Multidisciplinary Integration) to identify the most appropriate biomarkers for use in population studies. In addition to logistical and ethical considerations for conducting large-scale epidemiological studies, we discuss the relevance of their use for assessing the effects of low dose ionizing radiation exposure at the cellular and physiological level. We also propose a temporal classification of biomarkers that may be relevant for molecular epidemiology studies which need to take into account the time elapsed since exposure. Finally, the integration of biology with epidemiology requires careful planning and enhanced discussions between the epidemiology, biology and dosimetry communities in order to determine the most important questions to be addressed in light of pragmatic considerations including the appropriate population to be investigated (occupationally, environmentally or medically exposed), and study design. The consideration of the logistics of biological sample collection, processing and storing and the choice of biomarker or bioassay, as well as awareness of potential confounding factors, are also essential.

Cancer and non-cancer brain and eye effects of chronic low-dose ionizing radiation exposure.

BackgroundAccording to a fundamental law of radiobiology (“Law of Bergonié and Tribondeau”, 1906), the brain is a paradigm of a highly differentiated organ with low mitotic activity, and is thus radio-resistant. This assumption has been challenged by recent evidence discussed in the present review.ResultsIonizing radiation is an established environmental cause of brain cancer. Although direct evidence is lacking in contemporary fluoroscopy due to obvious sample size limitation, limited follow-up time and lack of focused research, anecdotal reports of clusters have appeared in the literature, raising the suspicion that brain cancer may be a professional disease of interventional cardiologists. In addition, although terminally differentiated neurons have reduced or mild proliferative capacity, and are therefore not regarded as critical radiation targets, adult neurogenesis occurs in the dentate gyrus of the hippocampus and the olfactory bulb, and is important for mood, learning/memory and normal olfactory function, whose impairment is a recognized early biomarker of neurodegenerative diseases. The head doses involved in radiotherapy are high, usually above 2 Sv, whereas the low-dose range of professional exposure typically involves lifetime cumulative whole-body exposure in the low-dose range of < 200 mSv, but with head exposure which may (in absence of protection) arrive at a head equivalent dose of 1 to 3 Sv after a professional lifetime (corresponding to a brain equivalent dose around 500 mSv).ConclusionsAt this point, a systematic assessment of brain (cancer and non-cancer) effects of chronic low-dose radiation exposure in interventional cardiologists and staff is needed.

Increased Breast Cancer Prevalence Among Female Orthopedic Surgeons

As a result of low-dose ionizing radiation exposure during clinical practice, female orthopaedic surgeons may be at increased risk for breast cancer. The 2009 American Academy of Orthopaedic Surgeons (AAOS) membership directory was used to mail a survey to all female AAOS fellows. Survey responses were collected between June 2009 and June 2010 among 505 (69.7%) of the eligible women. We calculated standardized prevalence ratios (SPRs) and 95% confidence intervals (CIs) by dividing the observed number of cancers among female orthopaedic surgeons by the expected number, based on the gender-specific, age-specific, and race-specific cancer prevalence statistics in the general U.S. population. We compared the distribution of breast cancer risk factors in our study population to that of the women in the 2007 California Health Interview Survey (CHIS, n=30,541). Twenty-four women reported a prior diagnosis of invasive cancer. Female orthopaedic surgeons had a prevalence of cancer that was 85% higher than that of the general U.S. female population (SPR 1.85, 95% CI 1.19-2.76). Orthopaedic surgeons in our study also had a statistically significant 2.9-fold higher prevalence of breast cancer compared to the general U.S. female population (SPR 2.9, 95% CI 1.66-4.71). Survey respondents had a higher prevalence of both protective and predisposing breast cancer factors compared to California women. Our findings confirm that breast cancer prevalence is elevated among female orthopaedic surgeons. Although further research is needed to determine the factors behind this population's hypothesized increased risk, taken together, our results and others suggest that the orthopaedic community consider educating current practitioners of the use of protective shielding and other modifiable breast cancer risk factors.

Hiatus in Infant Acute Leukemia Incidence rates in Belarus: Adaptation-to-Low-Dose-Radiation Phenomenon?

Abstract 507The question of whether child acute leukemia (ChAL) incidence has changed as a result of Chernobyl is of great scientific and public interest. Our initial report (Nature, 1993) showed no increase in the incidence rates (IR) of ChAL in Belarus in the whole group of children (0–14 y.o.) 5 years (1986 – 1991) after accident. This data were confirmed in several European countries. As concerns infant’s AL (0–1 y.o.), Petridou et al. reported 2.6 times increase of AL in Greek infants, exposed in utero to Chernobyl radiation. No significant difference in IR was found among children aged 1 – 4 y.o. or older. All epidemiological data concerning separate analysis of infant (0–1 y.o.) ChL was concentrated on the first decade after Chernobyl and no any systematic data is available after 1996. Since 1979 the occurrence of leukemia has been documented accurately through the Registry of Blood diseases. The patients had to be inhabitants of Belarus and were grouped by age at diagnosis. AL diagnostic accuracy was confirmed by the international experts. Rates were standardized directly to the standard world population. We present the age-cohort-period analyses of IR trends of ChAL from 1979 to 2006 in Belarus. It comprised 1077 ChAL cases (0–4 y.o.). Number of cases and equivalent doses of whole body radiation exposure was tabulated by age at diagnosis and period of observation (seven pre-accident years, 1979–1985) and post-accident 7-year periods: 1986–1992, 1993–1999 and 2000–2006.During first 7 years after the accident (1986–1992) the IR of infant AL (0–1 y.o.) increased significantly – from 49 (IR=4.33) before Chernobyl to 67 cases (IR=6.36) in 1986–1992 (RR=1.47; p=0.04). Older age group (1–4 y.o.) did not show any increase in ChAL rates. Following 7-years period (1993–1999) revealed the statistically significant decrease of incidence of infant leukemia: from 49 (IR=4.33) before Chernobyl to 16 cases (IR=2.29) in 1993–1999 years (RR=0.53; p=0.024). Surprisingly, during the next 7 years (2000–2006) we found a further decrease of the incidence of infant leukemia with only 3 cases (IR=0.47) in 7 years. It is highly significant when compared with 49 cases (IR=4.33) before Chernobyl (p= 0.0000053, RR=0.11) and 67 cases (IR=6.36) appeared during first 7 years following Chernobyl accident (p < 0.0000001, RR=0.04). As concerns the older group (1–4 y.o.) we did not find any decrease of IR into the second (1993–1999) and third (2000–2006) 7-year periods.Actually we are working on the next time period (2007–2010) and new upgraded data will be presented.Long-term analysis of incidence of post-Chernobyl childhood acute leukemia permitted to discover the biphasic dynamics of infant's AL incidence rate. Significant increase into the first 7-year period followed by dramatic decrease between year +8 and year + 21. From radiological point of view it is relatively simpler to explain the increase into the first 7 years, because ionizing radiation is one of the few exposures for which the casual relationship with childhood leukemia has been established. Much more difficult to explain following after decrease in incidence rate of infant leukemia in Belarus. Can we speculate about the “adaptation-to-radiation” mechanisms? Over the past decades the growing body of data from cell cultures, experimental animals and humans suggests that low-dose ionizing radiation may have some beneficial (hormetic or adoptive) effect. Several epidemiological studies (India, China, Japan, USA) of a long-term low dose environmental irradiation are in favor of the hypothesis of radiation hormesis or adaptation. The carcinogenic effects of low dose radiation exposure may be restricted to children exposed in utero or in early infancy (0-12 months) during the first years after explosion. Following after dramatic decrease of IRs of infant leukemia might be explained by the developing of adaptive response to chronic low dose ionizing radiation exposure. The presented data may be one of the first clinical evidence concerning human ability of adaptation to long-term low dose radiation. Disclosures:No relevant conflicts of interest to declare.

Exposure to Low-Dose Ionizing Radiation from Cardiac Imaging Among Patients With Myocardial Infarction

Patients with first acute myocardial infarction (AMI) constitute a demographic that is exposed to significant amounts of low-dose ionizing radiation (LDIR) over a short period. The aim of this study was to describe cardiac LDIR exposure trends among patients with first AMI over a recent approximately 10-year period. Administrative databases were used to identify a cohort of 106,803 patients who had first AMIs in Quebec, Canada, from 1996 to 2004. These patients were followed through 2007, and the use over time of cardiac imaging procedures associated with LDIR was documented using a cumulative exposure variable. Exposure was documented in 2 periods: the acute phase (<1 month after AMI) and the chronic phase (1 month to 3 years after AMI). The mean dose of cardiac LDIR incurred in the acute post-AMI phase increased twofold during the study period, from 6.8 to 11.8 mSv/patient. However, the mean dose of cardiac LDIR incurred in the chronic post-AMI phase decreased, from 8.3 to 7.3 mSv/patient. Overall, there was a 26.4% increase in cumulative cardiac LDIR exposure, to a mean of 19.1 mSv/patient in the 2 years after AMI, which was driven primarily by an increase in percutaneous coronary interventions. When patients were stratified by cumulative LDIR exposure, several predictors of heavier LDIR exposure were identified among the strata of exposed patients, including younger age and the absence of acute and co-morbid conditions, and the heaviest exposed group subsequently had the lowest overall mortality. In conclusion, among patients experiencing first AMI in Canada, exposure to cardiac LDIR increased over a recent approximately 10-year period. However, the observed trend is toward increasing use of therapeutic procedures with proven mortality benefit undertaken earlier in the disease course and away from diagnostic procedures in the subsequent years after AMI.

O2-1.4 Significant increase followed by dramatic decrease of infant leukaemia rates in Belarus: adaptive effect of low dose Chernobyl radiation?

The question of whether child acute leukaemia (ChAL) incidence in most contaminated countries has changed as a result of Chernobyl remains of great interest.We present results of age-cohort-period analyses of...

Alterations of ubiquitylation and sumoylation in conventional renal cell carcinomas after the Chernobyl accident: a comparison with Spanish cases

We determined whether ubiquitylation and sumoylation processes are involved in conventional renal cell carcinogenesis associated with chronic, long-term, persistent low doses of ionizing radiation (IR) in patients living for more than 20years in cesium-137 ((137)Cs)-contaminated areas after the Chernobyl accident in Ukraine. To this end, we assessed the immunohistochemical expression of ubiquitin (Ub), SUMO1, SUMO E2 conjugating enzyme Ubc9, and the cell cycle regulators p53, mdm2, and p14(ARF) in 38 conventional renal cell carcinomas from Ukrainian patients with different degrees of radiation exposure after the Chernobyl accident. As control cases, 18 conventional renal carcinoma (cRCC) tissues from a Spanish cohort were analyzed. No significant differences between the Ukrainian and Spanish groups were found regarding Ub overexpression, although being higher in the Ukrainian cases. Furthermore, this expression was inversely associated with SUMO1 and Ubc9, with no correlation with tumor nuclear grade. There was also a direct relationship between Ubc9 and inflammatory response. These findings do not allow us to consider the immunohistochemical expression of ubiquitylation and sumoylation as valuable markers for discriminating the effects of long-term, low-dose IR exposure in cRCC carcinogenesis.

Low dose ionizing radiation exposure can alter unmotivated mouse behavior and brain-based inflammatory mediators (116.34)

Abstract Individuals exposed to ionizing radiation (IR) experience acute radiation syndrome, the prodromal phase of which includes symptoms such as malaise and fatigue. These symptoms and related adverse biobehaviors have mental, physical and motivational elements that can be difficult to experimentally isolate. We’ve developed an experimental system to test IR-induced fatigue in mice using gamma rays to deliver total body IR in both motivated and unmotivated settings. 6h after a 50cGy dose of 137Cs whole body radiation, mice had a 34% reduction in spontaneous distance moved and average velocity of movement compared to non-irradiated mice. In contrast, the motivated behavior social exploration of a novel juvenile showed non-statistically significant trends toward reduced activity up to 6h post-IR. Examination of brain-based immunity showed whole brain TNF-α mRNA was significantly increased at 4 and 6h post-IR and this increase was coupled to 1) an up-regulation of IL-1RA and down-regulation of IL-6 mRNAs 4h post-IR and 2) a down-regulation of IL-1β, IFN-γ and F4/80 mRNAs at 6h post-IR. Together these data show that shortly after low-dose IR, mouse activity is reduced but can be overcome via a motivator. This altered locomotion is tied to a brain-based alteration in pro/anti-inflammatory balance. These data suggest anti-inflammatory therapies such as corticosteroids or anti-TNF/IL-1 agents may be effective countermeasures for prodromal symptoms due to IR exposure.

Diagnostic Imaging Is Common in Children

The rapid increase in diagnostic imaging has raised concern about low-dose ionizing radiation exposure in children. Two new studies shed light on this problem. In one study, investigators used claims data from a large national healthcare organization to determine how many diagnostic imaging procedures with ionizing …

Wavelet-SVM classification and automatic recognition of unstained viable cells in phase-contrast microscopy

Irradiation of individual cultured mammalian cells with a pre-selected number of ions down to one ion per single cell is a useful experimental approach to investigating the low-dose ionising radiation exposure effects and thus contributing to a more realistic human cancer risk assessment. One of the crucial tasks of all the microbeam apparatuses is the visualisation, recognition and positioning of every individual cell of the cell culture to be irradiated. Before irradiations, mammalian cells (specifically, Chinese hamster V79 cells) are seeded and grown as a monolayer on a mylar surface used as the bottom of a specially designed holder. Manual recognition of unstained cells in a bright-field microscope is a time-consuming procedure; therefore, a parallel algorithm has been conceived and developed in order to speed up this irradiation protocol step. Many technical problems have been faced to overcome the complexity of the images to be analysed: cell discrimination in an inhomogeneous background, among many disturbing bodies mainly due to the mylar surface roughness and culture medium bodies; cell shapes, depending on how they attach to the surface, which phase of the cell cycle they are in and on cell density. Preliminary results of the recognition and classification based on a method of wavelet kernels for the support vector machine classifier will be presented.

Biological effects of low-dose ionizing radiation exposure on interventional cardiologists

Interventional cardiologists (ICs) are likely to receive high radiation exposure as a result of procedures they undertake. To assess the effects of low-dose X-ray radiation exposure on chromosomal damage and on selected indices of cellular and humoral immunity in ICs. The study population consisted of 37 ICs and 37 clinical physicians as the control group with similar age, sex and duration of employment, without any work-related exposure to ionizing radiation. Cytogenetic studies were performed by chromosome aberration analysis and immunological studies by flow cytometry, enzyme-linked immunosorbent assay and immunodiffusion techniques. The frequencies of aberrant cells, chromosome breaks and dicentrics plus centric rings were significantly higher in the exposed group compared to the control group (P < 0.05; P < 0.01; P < 0.001, respectively), without positive correlation between the frequency of dicentric and centric ring aberrations and the cumulative doses of the ICs (r = 0.24, not significant). A significant increase was observed in the expression of activation marker CD69 on TCD4(+) stimulated cells in serum immunoglobulin G and interleukin (IL)-2 (P < 0.05) and a significant decrease in serum IL-10 (P < 0.05) in the ICs compared with that of the control group. There was no statistical difference between the two groups in terms of number of white blood cells and lymphocytes, CD3(+), CD4(+) and CD8(+) T cells, CD19(+) and CD16(+) 56(+) cells and concentrations of interferon (IFN)-gamma, IL-4, IL-6 and IL-8 cytokines. While cytogenetic results show higher chromosomal damage, some immune responses are stimulated or modulated immunologically in ICs.