Micronucleus Frequency In Lymphocytes Research Articles

Health risks of rare earth elements exposure: Impact on mitochondrial DNA copy number and micronucleus frequency

Toxic effects in terms of mitochondria and hereditary substances have been characterized in vitro for individual rare earth elements, while, the joint effects of mixed elements exposure in the population remain ambiguous. Based on the Occupational Chromate Exposure Dynamic Cohort of China, this study investigated the relationship between 15 blood rare earth elements (cerium, dysprosium, erbium, europium, gadolinium, holmium, lanthanum, lutetium, neodymium, praseodymium, samarium, terbium, thulium, yttrium, and ytterbium) and mitochondrial DNA copy number (MtDNACN) as well as peripheral blood lymphocyte micronucleus frequency (MNF). The elastic net was used to select elements highly correlated with effect indicators, whose dose-response relationships were further illustrated by restricted cubic splines. Bayesian kernel regression was employed to explore the combined effects of elements and the contributions of single element. The results showed that most rare earth elements were positively correlated with effect indicators, with yttrium showing the strongest association (β (95% CI): 0.139 (0.1089 – 0.189) for MtDNACN, 0.937 (0.345 – 1.684) for MNF). In the mixed exposure model, with the exposure level fixed at the 50th percentile as the reference, the effect estimates on MtDNACN and MNF increased by 0.228 and 0.598 units, respectively, at the 75th percentile. The single effect analysis implied that yttrium, lanthanum and terbium contributed the most to the elevation of MtDNACN, while yttrium posed the highest risk for genetic damage, accordingly, we provided recommendations to prioritize these elements of concern. In addition, we observed a chief mediating effect of MtDNACN on the elevation of MNF caused by lanthanum, whereas further mechanistic exploration is required to confirm this finding.

Genotoxic and cytotoxic effects of thiomersal and paracetamol combination

Background: Thiomersal is used as a preservative of some vaccines or as a trace from the pathogen inactivation process in vaccine production. Prophylactic use of paracetamol upon vaccination is still common, even though paracetamol decreases immune response on some vaccines. Considering the cytotoxic and genotoxic potential of thiomersal and paracetamol and possible interaction in vivo, in vitro study was performed. Methods: The genotoxic and cytotoxic effects of thiomersal and paracetamol combination were examined on human lymphocyte cultures by using two methods: analysis of chromosomal aberrations and cytokinesis-block micronucleus cytome assay. Blood samples of three healthy donors were analyzed with the following concentrations of tested substances: thiomersal 1 µg/ml and 0.5 µg/ml, paracetamol 20 µg/ml, thiomersal 0.5 µg/ml with paracetamol 20 µg/ml and thiomersal 1.0 µg/ml with paracetamol 20 µg/ml. Results: The analysis of structural chromosomal aberrations was significantly increased in all treated cultures. In cells treated with the combination of thiomersal 1 µg/ml and 20 µg/ml of paracetamol, the number of aberrations was significantly decreased. Cytokinesis-block micronucleus cytome assay analyses showed significantly increased micronucleus frequency in lymphocytes cultivated with thiomersal 1 µg/ml compared to lymphocytes cultures exposed to thiomersal 0.5 µg/ml. Conclusions: Induction of structural chromosome aberrations and micronucleus is shown as a sign of genotoxicity for the examined concentrations of thiomersal and paracetamol. The suppressing effect of paracetamol on thiomersal genotoxicity in lymphocytes culture treated with thiomersal was shown to be indicative of further examination of paracetamol use in the prevention of genotoxicity.

Cytokinesis-block micronucleus cytome (CBMN-CYT) assay and its relationship with genetic polymorphisms in welders

Fumes generated in the welding process are composed of micrometric and nanometric particles that form when metal fumes condense. The International Agency for Research on Cancer established that many compounds derived from the welding process are carcinogenic to humans. Still, there are few studies related to the role of genetic polymorphisms. This work aimed to analyze the influence of OGG1 Ser326Cys, XRCC1 Arg280His, XRCC1 Arg194Thr, XRCC1 Arg399Gln, XRCC3 Thr241Met, GSTM1, and GSTT1 gene polymorphisms on DNA damage of 98 subjects occupationally exposed to welding fumes and 100 non exposed individuals. The results showed that individuals exposed to welding fumes with XRCC3 Thr241Thr, XRCC3 Thr241Met, and GSTM1 null genotypes demonstrated a significantly higher micronucleus frequency in lymphocytes. In contrast, individuals with XRCC1 Arg399Gln and XRCC1 Gln399Gln genotypes had significant levels of NPBs. OGG1 326 Ser/Cys, OGG1 326 Cys/Cys, XRCC1 194Arg/Thr, XRCC1 194Thr/Thr, and GSTT1 null genotypes exhibited significantly higher apoptotic values. Also, XRCC1 194Arg/Trp, XRCC1 194Thr/Thr, and GSTM1 null genotype carriers had higher necrotic levels compared to XRCC1 194Arg/Arg and GSTM1 nonnull carriers. Compositional analysis revealed the presence of iron, manganese, silicon as well as particles smaller than 2 μm that adhere to each other and form agglomerates. These results may be associated with a mixture of components, such as nitrogen dioxide, carbon monoxide, and metallic fumes, leading to significant DNA damage and cell death processes. These findings demonstrated the importance of the association between individual susceptibility and DNA damage levels due to occupational exposure to welding fumes; and constitute one of the first studies carried out in exposed workers from Colombia.

Global and gene-specific promoter methylation, and micronuclei induction in lead-exposed workers: A cross-sectional study.

Perturbation of epigenetic regulation is a well-established mechanism for cancer but its role for lead (Pb)-associated toxicity has not been adequately investigated. We aimed to investigate whether occupational Pb exposure is associated with micronuclei (MN) frequency and to further explored the mediating roles of epigenetic gene regulation. All the Pb-exposed workers recruited from a Chinese acid battery factory, blood lead levels (BLLs) and MN frequency in lymphocytes were measured. In addition, methylation levels of seven genes (Line-1, RASSF1A, RUNX3, p16, CYP26C1, hMLH1, p15) were examined among 230 workers. Robust Poisson regression model was used to investigate the association between BLLs and MN frequency. Mediation analysis was used to explore the mediating role of specific DNA methylation. Among total 677 participants, 71% were male, median BLLs was 229.1μg/L (P25 = 155.5, P75 = 319.3; ranged from 8.9 to 647.7μg/L), mean MN frequency was 2.5‰ (SD = 1.8‰; ranged from 0 to 9‰). Results from base model, adjusted for age, sex, and body mass index, showed that MN frequency would increase 1.38 (95%confidential interval: 1.34, 1.43) per 100 μg/L increment in BLLs. Using categorized exposure variable analyses, a BLLs dose-response increase in MN frequency was observed: 2.74 (2.13, 3.51), 3.43 (2.73, 4.32), 4.41 (3.89, 5.01) to 6.86 (6.02, 7.81). Mediation analysis indicated that Line-1 methylation significantly mediated 3.6% of the association of BLLs with MN frequency. Occupational Pb exposure induces MN frequency in a dose-response relationship. Part of this association was mediated by Line-1 promotor methylation.

Effects of polycyclic aromatic hydrocarbons and multiple metals co-exposure on the mosaic loss of chromosome Y in peripheral blood

Mosaic loss of chromosome Y (mLOY) is an indicator of genome instability, but the environmental stressors of mLOY remained largely unknown. In this study, we detected the internal exposure levels of 11 polycyclic aromatic hydrocarbon (PAH) metabolites and 22 metals among 888 coke-oven workers, and calculated their blood mLOY based on genome-wide SNP genotyping data and presented as median log R ratio (mLRR-Y). The generalized linear model (GLM), LASSO, and Bayesian kernel machine regression (BKMR), were used to select mLOY-relevant chemicals. The results of these models consistently suggested the negative dose-response relationships of urinary 1-hydroxynaphthalene (1-OHNa), antimony (Sb), and molybdenum (Mo) with mLRR-Y. There were no pairwise interactions between these three chemicals (Pinteraction > 0.05), but subjects with high exposure to ≥ 2 kinds of these chemicals showed reducing mLRR-Y [β(95%CI) = − 0.015(− 0.023, − 0.008)], increasing oxidative DNA damage (marked by 8-hydroxydeoxyguanosine) [β(95%CI) = 0.625(0.454, 0.796)] and chromosome damage (marked by micronucleus frequency in lymphocytes) [frequency ratio (FR) and 95%CI = 1.146(1.047, 1.225)] than those with low exposure to all these chemicals. The combined effects of 1-OHNa, Sb, and Mo on elevating DNA damage may partly explain their joint effects on increased blood mLOY. These results provided a new insight into environmental hazards co-exposure on chromosome-Y deletions.

Biological Effects of Scattered Versus Scanned Proton Beams on Normal Tissues in Total Body Irradiated Mice: Survival, Genotoxicity, Oxidative Stress and Inflammation.

Side effects of proton therapy are poorly studied. Moreover, the differences in the method of dose delivery on normal tissues are not taken into account when proton beams are scanned instead of being scattered. We proposed here to study the effects of both modalities of proton beam delivery on blood; skin; lung and heart in a murine model. In that purpose; C57BL/6 mice were total body irradiated by 190.6 MeV proton beams either by Double Scattering (DS) or by Pencil Beam Scanning (PBS) in the plateau phase before the Bragg Peak. Mouse survival was evaluated. Blood and organs were removed three months after irradiation. Biomarkers of genotoxicity; oxidative stress and inflammation were measured. Proton irradiation was shown to increase lymphocyte micronucleus frequency; lung superoxide dismutase activity; erythrocyte and skin glutathione peroxidase activity; erythrocyte catalase activity; lung; heart and skin oxidized glutathione level; erythrocyte and lung lipid peroxidation and erythrocyte protein carbonylation even 3 months post-irradiation. When comparing both methods of proton beam delivery; mouse survival was not different. However, PBS significantly increased lymphocyte micronucleus frequency; erythrocyte glutathione peroxidase activity and heart oxidized glutathione level compared to DS. These results point out the necessity to take into account the way of delivering dose in PT as it could influence late side effects.

PIG-A gene mutation as a genotoxicity biomarker in human population studies: An investigation in lead-exposed workers.

The rodent Pig-a gene mutation assay has demonstrated remarkable sensitivity in identifying in vivo mutagens, while much less is known about the value of the human PIG-A assay for risk assessment. To obtain more evidence of its potential as a predictive biomarker for carcinogen exposure, we investigated PIG-A mutant frequencies (MFs), along with performing the Comet assay and micronucleus (MN) test, in 267 workers occupationally exposed to lead. Multivariate Poisson regression showed that total red blood cell PIG-A MFs were significantly higher in lead-exposed workers (10.90 ± 10.7 × 10-6 ) than in a general population that we studied previously (5.25 ± 3.6 × 10-6 ) (p < .0001). In contrast, there was no increase in lymphocyte MN frequency or in DNA damage as measured by percentage comet tail intensity in whole blood cells. Current year worker blood lead levels (BLL), an exposure biomarker, were elevated (232.6 ± 104.6 μg/L, median: 225.4 μg/L); a cumulative blood lead index (CBLI) also was calculated based on a combination of current and historical worker BLL data. Chi-square testing indicated that PIG-A MFs were significantly related to CBLI (p = .0249), but independent of current year BLL (p = .4276). However, % comet tail intensity and MN frequencies were better associated with current year BLL than CBLI. This study indicates that the PIG-A assay could serve as biomarker to detect the genotoxic effects of lead exposure and demonstrates that a battery of genotoxicity biomarkers having mechanistic complementarity may be useful for comprehensively monitoring human carcinogenic risk.

In vitro peripheral blood mononuclear cell proliferation, cytokine secretion and oxidative stress modulation by pyrido[2,3-d] pyrimidines

The aim of this work was to study the in vitro effects of new pyrido[2,3-d] pyrimidines, especially 4-(N-phenylethylamino)-5,7-diphenylpyrido[2,3-d] pyrimidine (3a) and 4-(N-benzylamino)-5-(4-chlorophenyl)-7-(3-methoxyphenyl) pyrido[2,3-d]-pyrimidine (3b), on the proliferative responses of human peripheral blood mononuclear cells, cytokine secretion, ATP levels and intracellular redox status. Peripheral blood mononuclear cells were isolated using differential centrifugation on a density gradient of Histopaque. These cells were cultured with the mitogen concanavalin A (Con A) and with different concentrations of the compounds 3a and 3b (1–100 µM). Proliferation (MTT assay), IL-2, INFγ and IL-4 (Elisa kits), ATP levels, cytotoxic effect (micronucleus test) and oxidative markers (intracellular glutathione, superoxide dismutase, catalase, hydroperoxide and carbonyl protein contents) were investigated after 48-h incubation. Our results showed that 3a was immunostimulant at low concentrations but immunosuppressive at high concentrations (50, 100 µM) with a modulation of cytokine secretion. 3b was immunostimulant in a dose-dependent manner. 3a induced an increase in intracellular ATP levels at 1–25 µM but a decrease at 50–100 µM. In the presence of 3b, cell ATP contents increased with 3b concentrations. Peripheral blood mononuclear cell redox markers were consistent with the presence of an oxidative stress induced by high concentrations of 3a and 3b, with a significant increase in the micronucleus frequency in lymphocytes, suggesting cytotoxic effects. However, 3a at low concentrations (1–25 µM) tended to activate antioxidant defense in cells. In conclusion, 3a and 3b modulate cell-mediated immunity, cell energy and redox status at low concentrations.

Micronucleus assay for monitoring the genotoxic effects of arsenic in human populations: A systematic review of the literature and meta-analysis.

The micronucleus (MN) assay has been used to determine the potential genotoxic effects in human populations exposed to arsenic. Some of these studies found an increase in MN frequency among exposed individuals, but others found no increase or inconclusive results. Thus, the main purpose of this current study was to investigate whether MN can be used as a biomarker for the arsenic exposure, as well as whether or not the different cell types that have been used to monitor MN frequency differ in their sensitivity to upon arsenic exposure. A systematic literature review was conducted followed by a meta-analysis. The review identified 25 useful studies with data from 3232 exposed individuals (15 studies assaying lymphocytes, 16 assaying buccal cells, and 9 assaying urothelial cells), with 18 studies measuring drinking water exposure, 5 measuring occupational exposure, one measuring coal burning, and one measuring dietary exposure. The meta-analysis indicated that the overall estimates of Mean Ratio (MR, defined as the mean value of the response in the exposed group divided by the mean value of the response in the reference group) were 2.95 (95% confidence interval (CI): 2.00 to 4.35), 2.36 (95% CI: 1.77 to 3.15), and 2.82 (95% CI: 1.86 to 4.28) for MN assays conducted with lymphocytes, buccal cells, and urothelial cells in the MN assay, respectively. Subgroup analysis showed that when the exposure method was drinking water, the MN frequencies increased significantly in lymphocytes (MR = 3.59, 95% CI: 2.30 to 5.60), in buccal cells (MR = 2.35, 95% CI: 1.76 to 3.15), and in urothelial cells (MR = 3.16, 95% CI: 2.02 to 4.97). However, when the exposure method was the occupational setting or others, the MN detection using the three types of cells did not find significant differences between groups. Subgroup analysis also showed that lymphocyte MN frequencies increased significantly in both routine-culture MN assays (MR = 2.88, 95% CI: 1.15 to 7.24) and cytokinesis-block MN assays (MR = 2.89, 95% CI: 1.84 to 4.55). The performance of the MN assay with different types of cells was also compared, but no significant differences were found. Therefore, our analysis indicates that MN can be used as an effective biomarker for monitoring arsenic-exposed populations, and that MN assays conducted with lymphocytes, buccal cells, and urothelial cells do not differ in their ability to detect the genetic damage from arsenic.

Cytotoxic and genotoxic effects in mechanics occupationally exposed to diesel engine exhaust

Diesel engine exhaust (DEE), which is the product of diesel combustion, is considered carcinogenic in humans. It comprises toxic gases, polycyclic aromatic hydrocarbons (PAHs) and particulate matter which can reach the pulmonary parenchyma and trigger various diseases, including cancer. The aim of the present study was to evaluate the potential cytotoxic and genotoxic effects of DEE exposure on peripheral blood and buccal epithelial cells in mechanics occupationally exposed to DEE. We recruited 120 exposed mechanics and 100 non-exposed control individuals. Significant differences were observed between the two groups in terms of percentage of tail DNA and damage index (DI) in the alkaline comet assay; levels of biomarkers by cytokinesis-block micronucleus cytome (CBMN-Cyt) assay; frequency of micronucleus (MN), nucleoplasmic bridge (NPB), nuclear bud (NBUD) and apoptotic cells (APOP) and levels of biomarkers for micronucleus, karyorrhexis (KRX), karyolysis (KRL) and condensed chromatin (CC) by the buccal micronucleus cytome (BM-Cyt) assay. A significant and positive correlation was found between the frequency of MN in lymphocytes and buccal cells in the exposed group. Also, there was a significant correlation between age and percentage of tail DNA and DI in the comet assay, APOP and MN in the CBMN-Cyt assay and NBUD and MN in the BM-Cyt assay. Additionally, we found a positive and significant correlation of MN frequency in lymphocytes and buccal cells and age and MN frequency in lymphocytes with the time of service (years). Regarding lifestyle-related factors, a significant correlation was observed between meat and vitamin consumption and NBUD formation on CBMN-Cyt and between meat consumption and MN formation on CBMN-Cyt. Of the BM-Cyt biomarkers, there was a correlation between alcohol consumption and NBUD formation and between binucleated cell (BN), pyknosis (PYC), CC and KRL occurrence and family cancer history. These results are the first data in Colombia on the cytotoxic and genotoxic effects induced by continuous exposure to DEE and thus showed the usefulness of biomarkers of the comet, CBMN-Cyt and BM-Cyt assays for human biomonitoring and evaluation of cancer risk in the exposed populations.

Micronucleus Cytome Assays in Human Lymphocytes and Buccal Cells.

The micronucleus (MN) assay, applied in different surrogate tissues, is one of the best validated cytogenetic techniques for evaluating chromosomal damage in humans. The cytokinesis-block micronucleus cytome assay in peripheral blood lymphocytes (L-CBMNcyt) is the most frequently used method in biomonitoring human populations to evaluate DNA damage caused by exposure to genotoxic agents, micronutrient deficiency or excess and genetic instability. Furthermore, recent scientific evidence suggests an association between an increased MN frequency in lymphocytes and risk of cancer and other age-related degenerative diseases. The micronucleus cytome assay applied in buccal exfoliated cells (BMNCyt), provides a complementary method for measuring DNA damage and cytotoxic effects in an easily accessible tissue not requiring ex vivo/in vitro culture. The protocol for L-CBMNcyt described here, refers to the use of ex vivo whole blood method, involving 72h of culture with the block of cytokinesis starting at 44h. BMNCyt protocol reports the established method for sample collection, processing, slide preparation and scoring.

Decreased Chromosomal Damage in Lymphocytes of Obese Patients After Bariatric Surgery

The number of bariatric surgeries being performed worldwide has markedly risen. While the improvement in obesity-associated comorbidities after bariatric surgery is well-established, very little is known about its impact on cancer risk. The peripheral lymphocyte micronucleus test is a widely used method for the monitoring of chromosomal damage levels in vivo, and micronucleus frequency positively correlates with cancer risk. Therefore, the aim of this study was to compare the micronucleus frequency before and after bariatric surgery in obese subjects. Peripheral blood mononuclear cells were collected from 45 obese subjects before and at two time-points after bariatric surgery (6 and 12 months) to assess spontaneous micronucleus frequency. Consistent with the increased cancer risk previously shown, bariatric surgery-induced weight loss led to a significant reduction in lymphocyte micronucleus frequency after 12 months. Interestingly, comorbidities such as type 2 diabetes mellitus and metabolic syndrome further seemed to have an impact on the lymphocyte micronucleus frequency. Our findings may indicate a successful reduction of cancer risk in patients following weight loss caused by bariatric surgery.

Frailty Syndrome and Genomic Instability in Older Adults: Suitability of the Cytome Micronucleus Assay As a Diagnostic Tool.

Frailty, a condition involving increased risk of disability and mortality in older adults, has emerged as a reliable way to predict the effect of aging. Genomic instability may help to anticipate recognition of frail individuals and improving frailty outcomes. Our objective was to evaluate the potential of the micronucleus frequency, evaluated in lymphocytes and buccal cells, to anticipate frailty identification and improve diagnosis reliability. Our results, from a group of older adults over 65, showed that frail individuals had significantly higher frequencies of micronucleus in lymphocytes (19.16 ± 0.66 vs. 13.07 ± 0.78, p < .001) and of binucleated buccal cells (82.65 ± 3.42 vs. 37.16 ± 2.85, p < .001) and lower frequencies of pyknotic and condensed chromatin buccal cells, than nonfrail subjects. When cognitive status was considered, similar results were obtained. Moreover, the presence of frailty and cognitive impairment were independently related to increases in frequencies of lymphocyte micronucleus and binucleated buccal cells. Our results encourage the use of micronucleus frequency in lymphocytes as a complement to clinical parameters in frailty identification. However, these results have to be further evaluated in prefrail patients, to better understand the connection between genomic instability and frailty and to establish these parameters as actual biomarkers of frailty in clinical practice.

Micronuclei frequencies in lymphocytes and cervical cells of women with polycystic ovarian syndrome.

Objective:The aim of this study was to determine micronucleus (MN) frequencies in exfoliated cervical cells and peripheral blood lymphocytes of women with polycystic ovarian syndrome (PCOS).Materials and Methods:Fifteen patients with PCOS and 11 healthy control patients were included in the study. Cervical smears and peripheral blood were collected from all patients. Specimens were analyzed for MN frequencies and compared between the groups. In addition to MN, other nuclear anomalies connected with both genotoxicity and cytotoxicity were evaluated.Results:The MN frequencies in cervical smear and peripheral blood lymphocytes were compared in patients with PCOS and normal controls. There was no statistically significant difference between the groups regarding micronucleus frequency in peripheral blood lymphocytes (p=0.239). The mean MN scores in exfoliated cervical cells of patients with PCOS and normal controls were 1.19±0.57 and 0.74±0.34, respectively. The difference regarding micronucleus frequencies in cervical cells was statistically significant between the groups (p=0.032).Conclusion:Although study group is small, our study results support that there is an increased micronucleus frequency in cervical exfoliated cells of PCOS patients; this is a determinant of genetic hazard in the disease.

Effect of CYP3A4 genetic polymorphisms on the genotoxicity of 4,4′-methylene-bis(2-chloroaniline)-exposed workers

ObjectivesWe investigated the relationship between 4,4’-methylene-bis(2-chloroaniline) (MBOCA) exposure and micronucleus (MN) frequency, and how this association was affected by genetic polymorphism of the cytochrome P450 enzyme (CYP3A4).MethodsWe divided the study...

A systematic review of the association between occupational exposure to formaldehyde and effects on chromosomal DNA damage measured using the cytokinesis-block micronucleus assay in lymphocytes.

Formaldehyde (FAL) is classified as a Class I carcinogen by the WHO International Agency for Research on Cancer. Therefore, there is a need to validate appropriate methods for detecting its genotoxic effects in vivo in humans. One of the most commonly used methods to measure the genotoxic effects of exposure to environmental chemicals is the lymphocyte cytokinesis-block micronucleus (L-CBMN assay). We performed a systematic review and statistical analysis of the results from all of the published studies in which the L-CBMN assay was used to measure the genotoxic effects of human exposure to FAL. The results of this systematic review indicated that the majority (62%) of the 21 investigations in the 17 published studies we examined showed significant increases in lymphocyte micronucleus (MN) frequency (a biomarker of chromosome breakage or loss), in exposed subjects relative to controls. We used a novel quality score tool to determine if the investigations adequately addressed known variables that affect MN frequency in lymphocytes and found that MN frequency was not explained by quality because there was no significant correlation between quality score and fold-change in MN frequency (R=0.008, P=0.97). The results of all of the studies (positive or negative), when combined together, indicated a highly significant doubling in lymphocyte MN frequency in those exposed to FAL relative to controls (P<0.0001). These observations, together with a significant positive correlation between L-CBMN assay MN frequency and FAL air concentration (R=0.529, P=0.017) indicate the suitability of this method to measure in vivo genotoxicity of FAL. Furthermore, fold-increase in lymphocyte MN frequency in the exposed subjects relative to controls was strongly positively correlated with the duration of FAL exposure (R=0.779, P<0.0001) suggesting the need to better understand the potential for cumulative genomic instability induced by chronic exposures to FAL.

Peripheral blood lymphocyte micronucleus frequencies in men from areas of Kerala, India, with high vs normal levels of natural background ionizing radiation

We have measured the frequencies of micronuclei (MN) in adult male individuals living in areas of the Kerala coast, southwest India, with either high (HLNRA, >1.5mGy/year) or normal levels of natural ionizing radiation (NLNRA, ≤1.5mGy/year). Blood samples were obtained from 141 individuals, 94 from HLNRA and 47 from NLNRA, aged 18–72, and were subjected to the cytokinesis-block micronucleus (CBMN) assay. An average of 1835 binucleated (BN) cells per individual were scored. The overall frequency of MN (mean±SD) was 11.7±6.7 per 1000 BN cells. The frequencies of MN in the HLNRA (11.7±6.6) and NLNRA (11.6±6.7) were not statistically significantly different (P=0.59). However, a statistically significant (P<0.001) age-dependent increase in MN frequency was observed among individuals from both HLNRA and NLNRA. No natural background radiation dose-dependent increase in MN frequency was seen. MN frequency was not influenced by tobacco smoking or chewing but it was increased among individuals consuming alcohol. Chronic low-dose radiation in the Kerala coast did not have a significant effect on MN frequency among adult men.

The assessment of micronucleus frequency in lymphocytes in the cohort of coal-miners characterized by different polymorphisms of double strand break reparation genes

Background: Coal-miners are exposed to a lot of number of harmful factors (chemical agents, ionizing radiation, heavy metals, coal dust etc.). Material and methods: Venous blood samples extracted from 129 coal-miners. Assessment of cytogenetic damage was performed using the cytokinesis-block micronucleus assay (CBMN) on peripheral blood lymphocytes. PCR and gel electrophoresis were used to determine polymorphisms in the genes Lig4 (rs1805388) and XRCC4 (rs6869366). Results: We found a significant increase in the frequency of binucleated lymphocytes with micronuclei (MN) and protrusions in carriers of the Ile/ Ile genotype of the Lig4 gene Thr9Ile polymorphism in comparison to Thr/Thr and Thr/Ile genotypes. Conclusions: Thr9Ile polymorphism within Lig4 gene can be used as potential molecular genetic markers of increased individual susceptibility to the complex of harmful factors in coal-mining conditions.

Outdoor air pollution exposures and micronuclei frequencies in lymphocytes from pregnant women and newborns in Crete, Greece (Rhea cohort)

BackgroundMicronuclei (MN) are biomarkers of early genetic effects that have been used to investigate the association between environmental exposures and cancer. However, few studies have examined the association between environmental exposures during pregnancy and MN in mothers and newborns. ObjectivesWe examined MN frequency in maternal blood and in cord blood, in relation to maternal air pollution exposure, and the potential interaction with maternal vitamin C intake and maternal smoking. MethodsWe used the cytokinesis-block micronucleus assay to assess MN frequency per 1000 bi-nucleated T-lymphocytes from 181 mothers and 183 newborns born in 2007–2008 in Heraklion (Crete, Greece). The ESCAPE land-use regression methods were used to estimate annual mean exposure to outdoor air pollution [particulate matter (PM), black carbon, nitrogen dioxide (NO2) and nitrogen oxides (NOx)] at maternal home addresses. Food frequency questionnaires were used to estimate maternal dietary vitamin C intake during pregnancy. Smoking habits were self-reported using questionnaires which were checked by measuring maternal urinary cotinine levels. ResultsExposure to PM2.5 was associated with increased MN frequencies in pregnant women [rate ratio [RR (95%CI)] per 5µg/m3=1.53 (1.02, 2.29)]. This increase was considerably higher among women who did not fulfill the recommended vitamin C dietary allowances [RR=9.35 (2.77, 31.61); n=20]. Exposure to PM2.5–10, PM10, NO2 and NOx were also associated with a higher incidence of MN frequencies in smoker women (n=56). No associations were found for newborns. ConclusionsWe found an association between air pollution, particularly PM2.5, and MN frequency in mothers but not in newborns. This association was more pronounced among women with a lower dietary intake of vitamin C during pregnancy and among women who smoked during pregnancy. While results are clear in mothers, the association between maternal carcinogenic exposures during pregnancy and biomarkers of early biologic effect in the newborn remains poorly understood.

Antineoplásicos e os riscos ocupacionais para os enfermeiros: uma revisão integrativa

Introducción: Son muchos los riesgos laborales a los que están expuestos los trabajadores de salud que manipulan quimioterápicos. &lt;br /&gt;&lt;br /&gt;Objetivos: Identificar y describir los daños a corto, medio y largo plazo, causados en el organismo de los enfermeros y otros profesionales de la salud, que están expuestos a los fármacos antineoplásicos en el lugar de trabajo. &lt;br /&gt;&lt;br /&gt;Metodología: Estudio de revisión integradora de la literatura, con la recogida de datos en la Biblioteca Virtual en Salud, en los meses de septiembre a octubre de 2013, en las bases de datos de biblioteca electrónica Scientific Electronic Library Online y en las bases de datos de la Literatura Latino Americana y Caribeña Ciencias de la Salud, la Base de Datos de Enfermería y el Análisis de la Literatura Médica y Recuperación del Sistema en Línea, con las palabras: “Antineoplasicos and Risco Ocupacional and Enfermagem”, “Antineoplastic and Occupational Risk” y “Antineoplastic and Nursing”.&lt;br /&gt;&lt;br /&gt;Resultados: Daño en el material genético, aumento de la frecuencia de micronúcleos en linfocitos, aumento de intercambio de cromátidas hermanas, un mayor nivel de la excreción urinaria antineoplásica, aumento de casos de cáncer, mayor incidencia de anomalías congénitas en la descendencia y aborto en el primer trimestre del embarazo son algunos de los resultados encontrados en este estudio. &lt;br /&gt;&lt;br /&gt;Conclusión: El daño más frecuente ocurre al ácido desoxirribonucleico, el predominio a medio y largo plazo, siendo el tiempo de exposición fundamental para aumentar el daño. A corto y largo plazo predominaron daños relacionado con el embarazo y el desarrollo fetal, con aumento de anomalías congénitas y aborto. Acompañamiento genético, así como equipos de protección individual son esenciales para minimizar los daños.&lt;br /&gt;&lt;br /&gt;