Higher Micronucleus Frequency Research Articles

Histopathological, cytotoxicological, and genotoxic effects of the semi-synthetic compound dillapiole n-butyl ether in Balb/C mice

ABSTRACT Dillapiole n-butyl ether is a substance derived from dillapiole, which exhibits potential insecticidal effects on Aedes aegypti, the principal vector of the Dengue fever, Zika, and Chikungunya viruses, as well as Aedes albopictus, a vector of Dengue fever. As these mosquitoes are resistant to synthetic insecticides, dillapiole n-butyl ether may represent a valuable, plant-based alternative for their control. Dillapiole n-butyl ether has insecticidal and genotoxic effects on A. aegypti and A. albopictus, as shown by the reduction in clutch size and egg viability, and increased mortality rates, as well as a high frequency of micronuclei and chromosomal aberrations. However, the potential cytotoxic and genotoxic effects of this substance in mammals are still unknown. In Balb/C mice, structural changes were detected in hepatic, renal, and cardiac tissues, which were directly proportional to the concentration of the dose applied, in both genders. The induction of genotoxic, mutagenic, and cytotoxic effects was also observed at the highest concentrations (150 and 328 mg/kg). Further research will be necessary to better characterize the potential genotoxicity of this substance at lower concentrations, for the evaluation of the potential health risks related to its presence in environmental features, such as drinking water.

Use of micronucleus assays for the prediction and detection of cervical cancer: a meta-analysis.

Cervical cancer (CC) is the fourth most common cancer in women; the survival rates depend strongly on its early detection. The Pap test is the most frequently used diagnostic tool, but due to its limited sensitivity/specificity, additional screening tests are needed. Therefore, we evaluated the use of micronucleus (MN) assays with cervical cells for the prediction and diagnosis of CC. MN reflects structural and numerical chromosomal aberrations. A search was performed in Pubmed, Scopus, Thomson ISI and Google Scholar. Subsequently, meta-analyses were performed for different grades of abnormal findings in smears and biopsies from patients which were diagnosed with CC. Results of 21 studies in which findings of MN experiments were compared with data from Pap tests show that higher MN frequencies were found in women with abnormal cells that are indicative for increased cancer risks. MN frequency ratios increased in the order inflammation (2.1) < ASC-US and ASC-H (3.3) < LGSIL (4.4) < HGSIL (8.4). Furthermore, results are available from 17 investigations in which MN were scored in smears from patients with neoplasia. MN rates increased with the degree of neoplasia [CIN 1 (4.6) < CIN 2 (6.5) and CIN 3 (10.8)] and were significantly higher (8.8) in CC patients. Our meta-analysis indicates that the MN assay, which is easy to perform in combination with Pap tests, may be useful for the detection/prediction of CC. However, standardization (including definition of the optimal cell numbers and stains) and further validation is necessary before the MN test can be implemented in routine screening.

Biomarkers of genotoxicity and health status of Rhinella fernandezae populations from the lower Paraná River Basin, Argentina

Abstract Anthropogenic activities may affect wild animal populations. Among them, amphibians are particularly sensitive to environmental change. The aim of this study was to evaluate the health condition of Rhinella fernandezae populations at three sites in the Buenos Aires Province, Argentina: a site inside a natural reserve (S1), a site surrounded mainly by industrial activities (S2) and a site surrounded principally by agriculture (S3). Sex and body condition (health status indicators), and micronuclei frequency (genotoxicity biomarker) of R. fernandezae adults were recorded to determine the health status of the local populations. Water samples were also analyzed for metals and pesticides to identify potential correlations with R. fernandezae malformations. Metals and pesticides were detected in the water samples of all three sites, with Al, Cu and Se exceeding the relevant limits for the protection of aquatic life. S1 had the highest overall environmental quality, and S2 had the greatest variety of pesticides. Individuals from S3 had significantly higher micronuclei frequency and females from S3 significantly lower body condition than females from S1, while females from S2 were significantly smaller than those from S1. Worst amphibian-based biological quality was assessed for S3, followed by S2 and S1. The low health status-fitness of females from the impacted sites (especially of the agriculture-surrounded S3 site), indicated by the low body condition and the high micronuclei frequency, may compromise the long-term health of the local amphibian populations. We conclude that action needs to be taken towards the long-term conservation of local amphibian populations from human-induced ecosystem degradation.

EVALUACIÓN DE LA CITOGENOTOXICIDAD DE UNA CERVEZA ELABORADA INDUSTRIALMENTE Y UNA CERVEZA DE ELABORACIÓN ARTESANAL

&lt;p class="Default"&gt;Beer is a complex beverage, due to the extended variety of dissolved constituents which interact with each other and may change rapidly from the moment of exposure to the environment. Much has been said about the impact on human health on the consumption of beer; excessive intake can lead to health problems, on the contrary with the moderate intake can significantly reduce DNA damage. The importance of short-term tests for carcinogens and mutagens (micronucleus test) is feasible to be applied in risk analysis and quality control of commercial alcohol beverages. The objective of this study was to evaluate the genotoxic effects in vivo of two different types of beers using &lt;em&gt;Vicia faba&lt;/em&gt;micronucleus test. Faba beans were used (&lt;em&gt;Vicia faba var. minor&lt;/em&gt;) that were exposed for 24, 48, 72 and 120 hours to the chemical composition of a mass-produced beer and craft beer. The cytogenotoxic effect from the beers was evaluated in root meristematic cells. Cycloheximide (5 &lt;em&gt;u&lt;/em&gt;g/ml), 3.6% ethanol (v/v) and 7.5% (v/v) were used as positive controls. Data were applied by analysis of variance with individual comparisons (Dunnett’s test) with a significance criterion of &lt;em&gt;p&lt;/em&gt;&amp;lt; 0.05. The results allowed toestablishing that treatments for the mitotic index and the frequency of micronuclei in meristematic cells had significant differences compared to the negative control. In conclusion, the chemical components of these alcoholic beverages and acetaldehyde derived from metabolized ethanol by the root neristematic cells of &lt;em&gt;V.faba&lt;/em&gt;did not induce high frequencies of micronuclei, in other words, they were slightly genotoxic and mildly toxic by decreasing or increasing of cell division on root meristem cells of &lt;em&gt;V. faba&lt;/em&gt;.&lt;/p&gt;

ASSESSMENT OF MICRONUCLEUS FREQUENCY AND RESPIRATORY HEALTH SYMPTOMS AMONG TRAFFIC POLICEMEN EXPOSED TO BTEX AND PM2.5 IN KLANG VALLEY, MALAYSIA

Volatile organic compounds such as benzene, toluene, ethylbenzene, xylene (BTEX), and particulate matter (PM) with a diameter of less than 2.5 microns (PM2.5) are often associated with traffic-related air pollution (TRAP) and harm the health of the community. This study aimed to evaluate the personal air pollutant exposure, micronucleus (MN) frequency, and respiratory health symptoms among 160 traffic policemen and 149 office workers in Klang Valley. Personal exposure concentrations for BTEX and PM2.5 among traffic police were 390.12 μg/m3 and 140.00 μg/m3 respectively, whereas 97.64 μg/m3 (BTEX) and 23.00 µg/m3 (PM2.5) among office workers. Statistical analysis for MN frequency between traffic policemen (6.2±2.6) and office workers (3.0±2.0) shows a significant difference (p &lt; 0.001). The Chi-Square test for respiratory health symptoms indicates that only cough shows the significant differences between traffic policemen and office workers (χ2 = 5.645, p = 0.018, PR = 1.800). In short, this study showed that TRAP exposure would increase the chromosomal damage that can cause high MN frequency among traffic policemen and would increase the prevalence of respiratory health symptoms among urban workers.

Detection of genotoxic effect of potassium permanganate by using in vitro micronucleus assay

Objective: Hydrogen peroxide is a bleaching agent accepted as safe for environment and used for producing cotton fabrics. This process requires alkaline medium, stabilizer and high temperature. For this purpose, it is used extensively in the textile industry. Potassium permanganate is a widely used agent in our country as it is easier to obtain compared to other oxidizing agents. In this study, we investigated whether occupational exposure to potassium permanganate causes genotoxic effect or not. Method: This cross-sectional study was carried out in a denim factory located in the Organized Industrial Zone in Sivas. The total number of employees was 600 in the factory including 50 workers in the office and 550 workers in the production department. The study group was consisted of 32 healthy males, non-smokers, without chronic diseases and infections. They had been working at least 2 years in denim bleaching unit. The control group was consisted of 30 healthy male volunteers, at similar age, non-smokers, working in administrative or desk jobs in the same factory, with little or no risk of chemical exposure. Workers who had an infection in the last month and who were on medication were excluded from the study. In Vitro Micronucleus Test was used to determine the genotoxic effect of potassium permanganate. The venous blood samples taken from the workers and controls was cultured in laboratory conditions according to Fenech’s method with minor modifications. Evaluation of slides was carried out according to Fenech’s microscopic survey criteria at ×1000 magnification. The frequencies of the total number of micronuclei in the lymphocytes (MNL) and bi-nucleated cells with the micronuclei (BNMN) were determined. In addition, to determine the frequencies of nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs), 1000 nucleated cells with well-preserved cytoplasm were also evaluated. Student’s T-test was used for statistical evaluation. Results: When groups were compared, the micronucleus frequency was detected as about twice high in study group. Statistically significant difference was detected between the study and control group (p 0.05). Conclusions: Indicators of genotoxic effect were higher in the group with potassium permanganate exposure than the control group. High micronucleus and nuclear bud frequencies in the study group may be indicative of genotoxicity. It may be thought that clastogenic and mutagenic risk increases for employees. Keywords: Potassium permanganate, micronucleus, nucleoplasmic bridge, nuclear bud, genotoxicity

Hypoxia reduced upper thermal limits causing cellular and nuclear abnormalities of erythrocytes in Nile tilapia, Oreochromis niloticus.

Global warming is a threat across the world that leads to estimates of the upper thermal limits of ectothermic species. Increased water temperature up-regulates oxygen consumption and metabolic rates, and alters the physiological processes. In this study, we identified the critical thermal maxima (CTmax) and physiological responses under normoxia and hypoxia in Nile tilapia, Oreochromis niloticus. CTmax was 41.25°C under hypoxia and 44.50°C under normoxia. Compared to normoxia, lower values of hemoglobin (Hb) and red blood cells (RBCs) were observed at the CTmax under hypoxia. In contrast, higher values of white blood cells (WBCs) and blood glucose (Glu) levels were observed at the CTmax under hypoxia. Consequently, higher frequencies of micronucleus, cellular and nuclear abnormalities of erythrocytes were observed at the CTmax under hypoxia. These results suggest that high temperature tolerance and subsequent physiology are significantly affected by the oxygen supply in Nile tilapia. As climate vulnerability is intensifying day by day, this data will be helpful in successful management practice for the aquatic environment having low oxygen content.

Antioxidant status and cytogenetic damage in hospital workers occupationally exposed to low dose ionizing radiation

The aim of the present study was to assess the oxidative stress level and chromosomal damage induced by occupational exposure to low dose ionizing radiation (LDIR). Two hundred and eighteen hospital workers occupationally exposed to LDIR were included in this study, along with 118 healthy age- and gender-comparable controls. Occupational dosimetry records were collected over the last year and revealed that the accumulated annual dose for each hospital worker was below the permissible limit of the International Commission on Radiological Protection (ICRP). The individuals’ oxidative and antioxidative status were determined by measuring the activities of copper zinc-superoxide dismutase (CuZn-SOD), glutathione peroxidase (GSH-Px), catalase (CAT) enzymes, and the levels of malondialdehyde (MDA) in erythrocytes. The effect of radiation on chromosomal integrity was measured by the frequency of micronuclei (MN) formation using the cytokinesis block technique. Our results showed that the activities of CuZn-SOD and CAT enzymes and MDA levels observed in the hospital workers were higher than those in the controls (p < 0.05). We did not find significant difference in GSH-Px enzyme activity between the two groups (p = 0.247). A higher frequency of MN was found in exposed groups than in the controls [3(1–5) ‰ versus 2(0.75–4) ‰; p<0.001]. The difference was significant for males (p = 0.012), but not females (p = 0.14). Multiple linear regression analysis showed differences in the oxidant activities and MN frequency between hospital workers and controls adjusted for age, gender, smoking status and drinking status. Correlation analysis indicated that the frequency of MN was positively associated with MDA levels (p < 0.05). Altogether, these results support the detrimental effects of chronic low dose radiation in humans, which involves the induction of oxidative stress and chromosomal damage.

Assessment of Listerine Cool Mint mouthwash influence on possible DNA damage measured by buccal micronucleus cytome assay-preliminary results

Listerine is a brand of mouthwash most used worldwide in oral hygene maintainance. With its antimicrobic and antifungal characteristics, it can stop/diminish plaque and gingivitis development. Among different types of this mouthwash, all 5 ingredients of Listerine Cool Mint, 21.6% ethanol and 4 herbal extracts-thymol, menthol, eucalyptol and methyl salicylate, have shown capacity to cause cell damage and buccal epithelial cells are in direct contact. Buccal micronucleus cytome assay (BMN) measures changes in differentiation as the frequency of basal/differentiated, binuclear, and cells in different phases of cell death-apoptosis/necrosis (cells with condensed chromatin, karriorhectic, pycnotic and karyolitic cells) and changes in genomic instability measured as micronucleus or nuclear buds/broken eggs frequency. Samples from 10 healthy individuals using Listerine Cool Mint mouthwash twice/day during two-week treatment were analyzed before and after the treatment. There was no significant influence on cell differentiation and genomic instability on the group level, although micronucleus frequency (MN) of entire group was higher after the treatment (1 vs. 1.5). We found interindividual differences and showed that strong alcoholic drinks consumers had higher MN. Future studies should include more individuals, especially with regular alcohol consummation for analysis of possible synergistic influence and therefore higher risk of genomic instability, together with genetic polymorphisms in enzymes responsible for metabolism of ethanol, since they can drastically influence the time duration of ethanol exposure and its metabolite acetaldehyde and also have an impact on genomic instability and possible development of oral squamous cell cancer.

Evidence of genotoxicity and cytotoxicity of X-rays in the oral mucosa epithelium of adults subjected to cone beam computed tomography.

Evidence of genotoxicity and cytotoxicity of X-rays in the oral mucosa epithelium of adults subjected to cone beam computed tomography.

CYTOGENETIC BIOMONITORING AND IMMUNOCYTOCHEMICAL STUDIES ON CAR SPRAY PAINTERS IN ENUGU METROPOLIS, ENUGU STATE, NIGERIA

Objective: This study assessed the cytogenetic damage associated with occupational exposure to paints by evaluating exfoliated buccal epithelial cells from car spray painters in Enugu metropolis using some biological markers.&#x0D; Methods: A total of 352 apparently healthy males, comprising 200 car spray painters and a control group of 152 individuals, participated in the study. Buccal smears were obtained from each participant and were stained using hematoxylin and eosin technique. A total of 1000 cells per individual were scored under light microscopy to determine the frequencies of micronuclei (MN) and binucleate cells (BNC). Structured questionnaires were used to obtain relevant participant information. Expression patterns of Ki-67and p53 genes on the buccal cells were determined by immunocytochemical methods.&#x0D; Results: Car spray painters had significantly increased frequencies of MN and BNC (*p&lt;0.05) when compared to the control subjects. Paint sprayers aged over 35 years had higher buccal cell MN frequency when compared to those &lt;25 years. Furthermore, car spray painters who have worked for ≥15 years had higher frequencies of MN when compared to those who had worked for &lt;5 years (*p&lt;0.05). Smoking and alcohol consumption increased the MN frequency of the car spray painters (*p&lt;0.05). There was no expression of p53 and Ki-67 genes in the buccal cells of both control and exposed subjects.&#x0D; Conclusion: Car spray painters in Enugu metropolis may be occupationally exposed to substances capable of inducing genotoxic changes which manifested as increased frequency of MN in their buccal cells.

Analysis of basal chromosome instability in patients with chronic lymphocytic leukaemia.

Genomic instability is a hallmark of cancer, contributing to tumour development and transformation, being chromosome instability (CIN) the most common form in human cancer. Chronic lymphocytic leukaemia (CLL) is the most frequent adult leukaemia in the Western world. In this study, we have evaluated basal CIN in untreated patients with CLL by measuring chromosome aberrations (CAs) and micronucleus (MN) frequency and their association with different prognostic factors. Seventy-two patients and 21 normal controls were analysed. Cytogenetic and fluorescence in situ hybridisation (FISH) studies were performed. IGHV (immunoglobulin heavy chain variable region) mutational status was evaluated by reverse transcription polymerase chain reaction and sequencing. An increased number of CA in patients compared with controls (P = 0.0001) was observed. Cases with abnormal karyotypes showed increased CA rate than those with normal karyotypes (P = 0.0026), with a particularly highest frequency in cases with complex karyotypes. Among FISH risk groups, a significant low frequency of CA was found in patients with no FISH alterations compared to those with del13q14 and ≥2 FISH alterations (P = 0.0074). When mean CA value (6.7%) was considered, significant differences in the distribution of low and high CA frequency between cases with normal and abnormal karyotypes (P = 0.002) were observed. By MN analysis, higher frequency in patients compared to controls (P = 0.0001) was also found, as well as between cases with ≥2 FISH abnormalities and those with no FISH alterations (P = 0.026). Similarly, significant differences were observed when patients were divided according to mean MN frequency (2.2%; P ≤ 0.04). Interestingly, patients with high MN frequency had shorter time to first treatment than those with low frequency (P = 0.024). Cases with mutated and unmutated IGHV status showed increased CA and MN frequencies compared to controls (P ≤ 0.0007), but no differences between both groups were found. Our results support the strong interaction between CIN and genomic complexity as well as their influence on poor outcome in this pathology.

Cytogenetic effects of radiation and genetic polymorphisms of the XRCC1 and XRCC3 repair genes in industrial radiographers.

Different types of DNA damages caused by ionizing radiation may enhance the cancer risk in exposed individuals. Inherited variations in DNA repair genes cause the inter-individual variability in response to ionizing radiation. The purpose of this study was to determine the association between single nucleotide polymorphism (SNP) of two important DNA repair genes (XRCC1 R399Q and XRCC3 T241M) and the level of DNA damage investigated by micronucleus (MN) frequency in peripheral blood lymphocytes of 120 industrial radiographers (IR) and 120 non-exposed control individuals. The frequencies of MN and nucleoplasmic bridges were significantly higher in the IR group than in the control group (33.83 ± 11.96 vs. 7.47 ± 2.96, p < 0.0001 and 1.69 ± 1.86 vs. 0.12 ± 0.33, p < 0.0001). MN frequencies in the IR group were associated with the cumulative radiation doses (p < 0.0001, r = 0.58 for last 1year of exposure and p < 0.0001, r = 0.67 for last 5years of exposure). Polymorphism of XRCC3 T241M was associated with higher MN frequencies in the IR group. However, the same result was not observed between XRCC3 SNP and MN frequency in the control group. Consequently, XRCC3 241Met alleles may cause the increased DNA damage in the industrial radiographers.

Evaluation of DNA Methylation Changes and Micronuclei in Workers Exposed to a Construction Environment.

Methylation levels in tumor-suppressor genes and repetitive sequences have previously been used to study the relationship between environmental air pollution and epigenetic changes related to cancer. In this study, we measured the methylation profiles of the promoter regions CDKN2A, MLH1 and APC and the repetitive sequence LINE-1 in 59 workers exposed to the construction environment and in 49 unexposed workers. We also evaluated the micronuclei frequency and levels of trace elements in the blood of all workers. We evaluated of levels of particulate matter and polycyclic aromatic hydrocarbons (PAHs) at the construction site to characterize the environmental exposure. Our findings demonstrated that exposed workers exhibited significantly higher average levels of promoter methylation of CDKN2A, APC, and MLH1 genes and increased hypomethylation of the LINE-1 in comparison to unexposed workers (all p < 0.05). A higher frequency of micronuclei was observed in the exposed group (2 ± 2) compared to the unexposed group (1 ± 1) with p < 0.001. High levels of particulate matter (51–841 μg/m3) and some PAHs were found in samples from the construction environment. In summary, we provide evidence of increased DNA damage and altered DNA methylation of exposed workers, suggesting that genomic approaches to biomonitoring may be an effective way of estimating future cancer risk for construction workers.

Effect of temperature on triclosan toxicity in Pangasianodon hypophthalmus (Sauvage, 1878): Hematology, biochemistry and genotoxicity evaluation

The rising level of triclosan (TCS) in aquatic environment is raising concerns and in this context, evaluation of toxicity towards aquatic organisms under varying environmental conditions, especially temperature, is a pre-requisite for a better understanding of the toxic effects on specific metabolic processes. In this report, the mechanistic physiological responses of fish towards varying concentration of TCS at graded temperature were evaluated. The static renewal acute test was performed, and 96 h median lethal concentration (LC50) of TCS for Pangasianodon hypophthalmus was estimated and the values were 848.33, 1181.94 and 1356.96 μg L−1 at 25, 30 and 35 °C respectively. The chronic study was performed for 30 days at 1/5th and 1/10th concentration of the estimated LC50 of TCS at 25, 30 and 35 °C respectively. The chronic effects resulted in significant decrease in total erythrocyte count (TEC), hemoglobin (Hb), packed cell volume (PCV), mean corpuscular hemoglobin (MCH) and mean cell volume (MCV), while a significant increase in total leukocyte count (TLC), mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW) was observed in TCS exposed groups at 25–35 °C. Further, a significant increase in activity of transaminase enzymes, lactate dehydrogenase (LDH) and antioxidant enzymes (superoxide dismutase) (SOD) and catalase (CAT) except glutathione-S-transferase (GST) in liver and acetylcholinesterase (AChE) in brain of the TCS exposed fish was recorded in all the above temperature range. Severe damage of DNA in nucleus of blood and liver cells, and high micronuclei frequency (MNi) was noticed in TCS exposed groups at 25 °C. The report provides convincing evidence for the effect of temperature on TCS toxicity. The findings will help in gaining a better insight into the change in toxicity of TCS in a natural environment where diurnal variations in temperature may be crucial in determining the overall extent of toxicity.

Genotoxic and mutagenic assessment of spinosad using bioassays with Tradescantia pallida and Drosophila melanogaster

Spinosad (SPN) is a naturally-occurring insecticide obtained from the fermentation process of the actinomycete Saccharopolyspora spinosa. Owing to the larvicidal action, the compound has been used in the control of Aedes aegypti. As a new insecticide commercially available in the market, few data are reported on genotoxic effects in non-target organisms. The objective of the present study was to evaluate the mutagenic effect of SPN through the Micronucleus Test in Tradescantia pallida (Trad-MCN) and using the mutation and somatic recombination test in Drosophila melanogaster (SMART). At the Trad-MCN, after acclimatization (24 h), T. pallida stems were submitted to chronic treatment with SPN at concentrations of 0.156; 0.312; 0.625; 1.25 and 2.5 g/L solution for 24 h, followed by a recovery period. In SMART, considering the third stage larvae, offspring resulting from the ST and HB crossing were placed on chronic treatment (48 h) with 0.039; 0.078 and 0.156 μg/mL of SPN solution. No mutagenic effect was observed at any of the evaluated concentrations in SMART. Additionally, SPN is more toxic after metabolism via CYP6A2 (cytochrome P450) in D. melanogaster. However, SPN at the concentrations of 0.625; 1.25 and 2.5 g/L was able to induce high frequency of micronuclei in T. pallida. Under the experimental conditions of T. pallida in the present study, SPN caused genotoxic activity.

Association of BER and NER pathway polymorphism haplotypes and micronucleus frequencies with global DNA methylation in benzene-exposed workers of China: Effects of DNA repair genes polymorphisms on genetic damage

ObjectiveThe base excision repair (BER) pathway and nucleotide excision repair (NER) pathway play important roles in the repair of benzene-induced genetic damage, and the effects of polymorphisms in these pathways on genetic damage and global DNA methylation are of great interest. MethodsTen single nucleotide polymorphisms (SNPs) in the BER (XRCC1: rs25489, rs25487; APE1: rs1130409) and NER pathways (XPA: rs1800975; XPC: rs2228000, rs2228002; XPD: rs13181, rs1799793; XPG: rs17655; ERCC1: rs3212986) were analyzed by a Kompetitive allele-specific PCR (KASP) assay to find associations with cytokinesis-block micronucleus (MN) frequency and global DNA methylation in 294 shoe factory workers and 102 control participants. ResultsWorkers who possessed the following genotypes were associated with high MN frequency: rs25487 AA (FR (95% CI): 1.50 (1.16,1.9), p = 0.002, reference GG); rs1130409 GG (FR (95% CI): 1.28 (1.05,1.55), p = 0.010, reference TT); rs17655 GC (FR (95% CI): 1.18 (1.02,1.38), p = 0.038, reference GG); and rs3212986 TT (FR (95% CI): 1.55 (1.31,1.83), p < 0.001, reference GG). Workers with four and three mutant alleles showed 3.72-fold (OR (95% CI): 3.72 (1.34, 10.03), p = 0.009) and 2.48-fold (OR (95% CI): 2.48 (1.27, 4.88), p = 0.008) increased risk of genetic damage compared with workers with no or one mutant allele, and a dose-response relationship was found by the trend test (p = 0.006). The rs1130409 variant allele (GG+GT) was associated with low global DNA methylation (β=-0.20, 95% CI: −0.42, 0.03, p = 0.045). ConclusionIn benzene-exposed workers, BER and NER pathway polymorphism haplotypes are associated with different levels of chromosome damage and had little effect on global DNA methylation.

Micronuclei frequency in peripheral blood lymphocytes and levels of anti-p53 autoantibodies in serum of residents of Kowary city regions (Poland) with elevated indoor concentrations of radon

IntroductionNinety four residents of Kowary city (Poland) have been investigated for environmental radon exposure that ranged from 0.24 WLM to 9.6 WLM (activity concentration range: 35–2700 Bq/m3). Kowary was chosen because of uranium mineralisation in its close vicinity. MethodWhole population studied was divided into two groups: exposed to low radon activity concentrations resulting in the exposure of ≤0.55 WLM (value corresponding to the exposure to 100 Bq/m3 during whole year), and exposed to high radon activity concentration (>0.55 WLM). In the two groups two selected biomarkers in blood were assessed: the cytokinesis-block micronucleus assay (CBMN) on peripheral blood lymphocytes (PBL), and the levels of anti-p53 antibodies in serum measured because some data indicate increased expression of the antibodies in individuals after exposure to DNA damaging agents including radon. The potential confounding factors known to influence micronuclei (MN) frequency were also measured in serum: vitamin B12, folic acid, as well as total calcium. ResultsIn the present study no significant correlation was found between MN frequency in PBL and radon exposure. Among all persons investigated only 11 had detectable levels of the anti-p53 antibodies, whereas only 3 persons had positive result. Therefore, the group was too small to perform any meaningful statistical analysis and to conclude on any association. Cigarette smoking did not significantly influence the number of MN. There was a significant positive correlation observed between MN frequency and age, as well as higher MN frequency was detected in women. ConclusionThe problem of the radon exposure is still unresolved and needs further studies on bigger human cohorts in order to search for more sensitive biomarkers.

Hunter syndrome: Long-term idursulfase treatment does not protect patients against DNA oxidation and cytogenetic damage

Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is an inborn error of metabolism characterized by the accumulation of glycosaminoglycans (GAG) in lysosomes. Enzyme replacement therapy (ERT) can reduce GAG storage, ameliorate symptoms, and slow disease progression. Oxidative damages may contribute to the MPS II pathophysiology, and treatment with ERT might reduce the effects of oxidative stress. We evaluated levels of DNA damage (including oxidative damage) and chromosome damage in leukocytes of long-term-treated MPS II patients, by applying the buccal micronucleus cytome assay. We observed that, despite long-term ERT, MPS II patients had higher levels of DNA damage and higher frequencies of micronuclei and nuclear buds than did control. These genetic damages are presumably due to oxidation: we also observed increased levels of oxidized guanine species in MPS II patients. Therapy adjuvant to ERT should be considered, in order to decrease oxidative damage and cytogenetic alterations.

Cytological observation of chromosome breakage in wheat male gametophytes caused by gametocidal action of Aegilops triuncialis-derived chromosome 3Ct.

In this study, we investigated the chromosome breakage caused by gametocidal (Gc) chromosome 3Ct and its interaction with the suppressor gene Igc1 (inhibitor of gametocidal gene 1) on wheat chromosome 3B. We demonstrated cytologically that patterns of 3Ct-induced chromosomal fragmentation in microspores differed from patterns observed for other Gc genes. Uninuclear microspores of the monosomic 3Ct addition line had high frequencies of micronuclei, possibly explaining its low fertility. Chromosome fragmentation was observed in prometaphase and metaphase of the first pollen mitosis in the monosomic 3Ct addition line. Patterns of chromosome fragmentation were different from those previously reported for Gc chromosomes 2S of Aegilops speltoides, 4Ssh of Ae. sharonensis and 2Ccy of Ae. cylindrica; many chromosome fragments were observed in prometaphase of the first pollen mitosis in the monosomic 3Ct addition plants. In anthers at the binuclear stage, many microspores at the uninuclear stage coexisted with normally developed microspores.