Occupational exposure to radiation among health workers: Genome integrity and predictors of exposure.

The current study aimed to investigate genomic instabilities in healthcare workers who may experience varying levels of radiation exposure through various radiological procedures. It also sought to determine if factors related to the work environment and dosimeter reading could effectively explain the observed genomic instabilities. Utilizing the cytokinesis-block micronucleus assay (CBMN) on peripheral blood lymphocytes, we assessed a spectrum of genomic aberrations, including nucleoplasmic bridge (NPB), nuclear budding (NBUD), micronucleus (MN) formation, and total DNA damage (TDD). The study uncovered a statistically significant increase in the occurrence of distinct DNA anomalies among radiology workers (with a significance level of P < 0.0001 for all measurements). Notably, parameters such as total working hours, average work duration, and time spent in projection radiography exhibited significant correlations with MN and TDD levels in these workers. The dosimeter readings demonstrated a positive correlation with the frequency of NPB and NBUD, indicating a substantial association between radiation exposure and these two genomic anomalies. Our multivariable models identified the time spent in projection radiography as a promising parameter for explaining the overall genomic instability observed in these professionals. Thus, while dosimeters alone may not fully explain elevated total DNA damage, intrinsic work environment factors hold potential in indicating exposure levels for these individuals, providing a complementary approach to monitoring.

Assessment of genetic damage induced by gadolinium-based radiocontrast agents.

BACKGROUND: Today, although gadolinium based contrast agents have been frequently used in the field of medicine, there is limited data available whether gadolinium based agents affect the genome. AIM: The present study aimed to investigate the genotoxic and cytotoxic potentials of gadoteric acid and gadoversetamide used as gadolinium-based contrast agents for magnetic resonance (MR) imaging. MATERIAL AND METHODS: The cytokinesis-block micronucleus assay was applied to human peripheral blood lymphocytes to assess the genotoxicity measured as micronucleus (MN), nucleoplasmic bridge (NPBs) and nuclear bud (NBUDs) frequencies. Furthermore, cytokinesis-block proliferation index (CBPI) was calculated to determine cytostasis. Lymphocytes were treated with gadoteric acid at concentrations of 1.0, 2.5, 5.0, and 25 mM and with gadoversetamide at concentrations of 0.25, 1.0, 2.5, and 5.0 mM for 48 h. RESULTS: Gadoteric acid did not cause significant increase in MN, NBPs and NBUDs frequencies and CBPI values at any concentration. Gadoversetamide induced significantly increase MN formation at concentration of 2.5 mM, NBP formation at concentrations of 1.0 and 2.5 mM, and NBUD formation at concentrations of 0.25, 1.0 and 2.5 mM. Additionally, gadoversetamide exposure resulted in statistically significant decrease in CBPI values compared to the control at concentrations of 2.5 and 5.0 mM. In addition, CBPI levels in response to concentrations of gadoversetamide was negatively and significantly associated with concentration. CONCLUSION: These findings show that gadoteric acid does not have genotoxic or cytotoxic potential, while gadoversetamide might have both genotoxic and cytotoxic potential on human peripheral blood lymphocytes. As a comparison, gadoversetamide was found more genotoxic and cytotoxic.

Assessment of the genotoxic potential of tetrachlorvinphos insecticide by cytokinesis-block micronucleus and sister chromatid exchange assays.

Tetrachlorvinphos is an organophosphate that is classified as a carcinogen in humans by several authorities. Due to very limited data regarding the genotoxic potential, we aimed to comprehensively investigate in vitro genotoxic potential of tetrachlorvinphos. We performed our study by applying the cytokinesis-block micronucleus cytome and sister chromatid exchange (SCE) assays to human peripheral blood lymphocytes. We evaluated micronucleus (MN) and SCE frequencies and cytokinesis-block proliferation index in both exposed and non-exposed lymphocytes. We also calculated the chromosomal instability level in response to exposure by combining the results of MN and SCE. We found that MN frequency did not increase with exposure to tetrachlorvinphos (0-50 µg/ml). In contrast, we observed that SCE frequencies significantly increased with exposure to ≥5 µg/ml tetrachlorvinphos. Furthermore, exposure to tetrachlorvinphos at concentrations of 50 µg/ml induced a significant increase in chromosomal instability level (p < 0.05). Cytokinesis-block proliferation index level did not significantly decrease in response to tetrachlorvinphos exposure. Our findings reveal that tetrachlorvinphos resulted in different DNA damages that were measured by two assays. Furthermore, our findings suggested that exposure to tetrachlorvinphos increased chromosomal instability that is a hallmark of many malignancies. We conclude that although tetrachlorvinphos does not significantly increase the MN level, the significant increase of both SCE and CIN frequencies indicates the genotoxic potential of tetrachlorvinphos in human peripheral lymphocytes. Additionally, tetrachlorvinphos is not cytotoxic in the range of tested concentrations.

Evaluation of DNA damages in congenital hearing loss patients.

In the current study, we aimed to compare the level of genetic damages measured as micronucleus (MN), nucleoplasmic bridge (NPB), and nuclear bud formation (NBUD) in congenital hearing loss patients (n = 17) and control group (n = 24). The cytokinesis-blocked micronucleus assay (CBMN) was applied to the blood samples to measure the frequency of the markers in both groups. The frequencies of MN of hearing loss patients were found to be consistently significantly higher than those obtained for the control group (p < 0.0001). Similarly, we found significantly higher frequency of NPB in patients was obtained for the patient group (p < 0.0001). Finally, the frequencies of NBUD in patients is significantly higher than the level measured in the control group (p < 0.0001). Furthermore, the age-adjusted MNL, BNMN, NPB, and NBUD frequencies in the patients were significantly higher than those obtained in the control group. We observed that the frequency of MN in patients was positively correlated with NBUD frequency which may indicate a common mechanism for these biomarkers in the patient group. We found, for the first time, that there were statistically significant higher levels of MN, NPB, and NBUD in sensorineural hearing loss patients. Since the markers we evaluated were linked with crucial diseases, our findings might suggest that sensorineural hearing loss patients are susceptible to several crucial diseases, especially cancer. Furthermore, the results demonstrated the significance of the MN, NPB, and NBUD level and thus provides a potential marker for the diagnosis of congenital hearing loss patients.

Genotoxic and cytotoxic effects of polyethylene microplastics on human peripheral blood lymphocytes.

Currently, we need emerging initial data regarding how plastic exposures affect cellular and molecular components and how such interactions will be crucial for human health. We aimed to determine the genotoxic and cytotoxic effects of microplastic (MPs,10-45 µm, polyethylene) on human peripheral lymphocytes by using the cytokinesis-block micronucleus cytome (CBMN) assay, which is a comprehensive method to reveal a range of mechanisms, not only diseases but also response to environmental exposures. We measured micronucleation (MN), nucleoplasmic bridge formation (NPB), and nuclear bud formation (NBUD) in human peripheral blood lymphocytes. We also measured the cytokinesis-block proliferation index (CBPI) to calculate cytostasis, which indicates cytotoxicity in lymphocytes treated with five different MPs concentrations for 48 h. Even lower concentrations of MPs increased the level of genomic instability. We found that the in vitro MP exposure significantly increased MN, NPB, and NBUD frequencies. Since we investigated the effect of larger particles relative to the lymphocytes, mechanic interaction of MPs with cells, the release of monomer and additives from MPs could be suggested as possible mechanisms accounting for increasing genomic instabilities. We did not observe a decrease in the cell proliferation index, indicating a lack of MPs' cytotoxic potential. To the best of our knowledge, our study is the first to identify MPs' genotoxic potential in human peripheral blood lymphocytes. We suggested further studies to investigate the genotoxic and cytotoxic potential of smaller plastics and the chronic effect of MP on the human population.

Different working conditions shift the genetic damage levels of pesticide-exposed agriculture workers.

In the current study, we had two main purposes. Firstly, we aimed to compare genetic damages in the agricultural workers of two different types of environmental conditions including the greenhouse and open fields. Secondly, we aimed to compare genetic damages in the total agricultural workers as the exposed group (greenhouse and open field workers) (n = 114) and the non-exposed control group (n = 98) living in the same area in Canakkale, Turkey. For these purposes, we investigated the incidence of micronucleus (MN), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs) in peripheral blood lymphocytes. We observed that the frequencies of MN, NPB, and NBUD obtained for the greenhouse workers were statistically significantly higher than those obtained for the open field workers. When the results of the control group were compared with those of the total workers, there were statistically significant differences in terms of MN and NBUD frequencies. We found that age and MN were correlated at a significant level in both the agricultural workers and the control group. The MN frequency of the female workers was 1.5 times greater than that of the male workers, and it was a significant level in the agricultural workers.

Assessment of the genotoxic potential of a migraine-specific drug by comet and cytokinesis-block micronucleus assays.

Background: Eletriptan is a migraine-specific drug-containing the triptan group. In terms of drug safety, the present study aimed to investigate the genotoxic potential of eletriptan.Research design & methods: We conducted our study by using the cytokinesis-block micronucleus cytome (CBMN) assay, a comprehensive method for measuring micronucleus formation, and a sensitive method for detecting DNA-strand breaks. In the assay, cytokinesis-block proliferation index and the frequency of micronuclei were evaluated in lymphocytes treated with three different concentrations (1, 10 and 25 µg/ml) of eletriptan for 48 hours. In comet assays, DNA damage was evaluated in leucocytes treated with three different concentrations (1, 10 and 25 µg/ml) of eletriptan for an hour.Results: Eletriptan did not induce cytotoxicity nor any increased micronuclei frequencies. While the comet parameters % DNA in tail, tail moment, and the olive moment was found to be significantly increased at 10 and 25 µg/ml, the cytokinesis-block proliferation index values were not.Conclusion: These findings suggest that eletriptan is non-cytotoxic but potentially weakly genotoxic at higher concentrations (10 and 25 µg/ml).

Results of buccal micronucleus cytome assay in pesticide-exposed and non-exposed group.

Since many different pesticides have been used occupationally, there have been inconsistent results regarding DNA damages among greenhouse workers. Thus, the aim of the study is to evaluate DNA damages, cell death, and chromosomal instability by using the buccal micronucleus cytome (BMcyt) assay in greenhouse workers and to compare those with a non-exposed group. The BMcyt assay was applied to the exfoliated buccal cell samples collected from 66 pesticide-exposed and 50 non-exposed individuals. We evaluated the frequency of micronucleus (MN), nuclear bud (NBUD), binucleated (BN) cells, and karyolitic (KL), pyknotic (PY), and karyorrhectic (KH) cells. The results showed that the MN, BN, PY, and KH frequencies of the pesticide-exposed group were significantly higher than those of the controls (P Ë‚ 0.05, P Ë‚ 0.05, P Ë‚ 0.01, and P Ë‚ 0.05, respectively). We observed that the MN, BN, PY, and KH frequencies in the autumn were statistically different compared with those in the control group (P = 0.037 for MN, P = 0.001 for BN, P = 0.016 for PY, and P = 0.033 for KH). The same comparison was done in the spring for the control, and there was a statistically significant difference for MN (P = 0.046) and PY (P = 0.014). We can conclude that pesticide exposure in greenhouse workers was one of the factors that altered DNA damages, cell death, and chromosomal instability in oral mucosa cells.

Comet assay for assessment of DNA damage in greenhouse workers exposed to pesticides.

Purpose: The main goal of the present study was to determine DNA damage in pesticide-exposed greenhouse workers and pesticides non-exposed controls. Materials and methods: The DNA damage was measured by alkaline comet assay method (pH > 13) in 41 greenhouse workers and 45 non-exposed individuals as the control. Pesticide exposure was assessed by duration of working in the greenhouse and pesticide application in the greenhouse time. DNA damage was estimated by arbitrary unit and damage frequency. Results: Arbitrary unit and damage frequency were consistently significantly higher in greenhouse workers than those of the controls (p = 0.001). In terms of gender in greenhouse, DNA damage of female workers was significantly higher than those in male workers (p < 0.05). We found significant correlation between DNA damage and working hours spent. Multiple linear regression analysis showed that working hours in the greenhouse as an indication of pesticide exposure were significantly associated with the DNA damage, which can be attributed to the genotoxic potential of the pesticide mixture. Conclusions: The comet assay is sensitive to detect the damage exposed to chronic effect of pesticides in greenhouse workers. Significant DNA damage was obtained for the exposed group, which was associated with the pesticide exposure.

DNA damage and circulating cell free DNA in greenhouse workers exposed to pesticides.

Pesticides widely used in agriculture and other applications have been linked to cancer and other diseases through several potential mechanisms. The goals of this study were to assess DNA damage in lymphocytes by the cytokinesis-block micronucleus assay (CBMN), and to measure circulating cell free DNA (ccf-DNA) in the blood of pesticide-exposed greenhouse workers and matched controls living in the same area. CBMN was applied to peripheral blood lymphocyte samples taken at different times (spring and autumn) for each individual. We measured plasma ccf-DNA levels using a Qubit® fluorometer. The results indicated that the MNL, BNMN, and NBUDs frequencies of pesticide-exposed individuals were significantly higher than non-exposed individuals. Apart from MNL, BNMN and CBPI, a season-related effect was found for the NPB and NBUD frequencies. With MNL and BNMN as the dependent variables, multiple regression analysis showed that age and gender affected MN formation. The ccf-DNA level in the pesticide-exposed group was significantly higher than the control group. There was no seasonal variation regarding the free DNA amount. Ccf-DNA in males was found to be higher than females. The MNL, BNMN, NPB, and CBPI did not correlate with the ccf-DNA amount. It can be concluded that pesticide exposure can modulate DNA integrity via different mechanisms. Also, elevated levels of ccf-DNA could be recommended as a biomarker of pesticide exposure. Environ. Mol. Mutagen. 59:161-169, 2018. © 2017 Wiley Periodicals, Inc.

In vitro genotoxic and cytotoxic effects of doxepin and escitalopram on human peripheral lymphocytes.

Antidepressants are drugs used for the treatment of many psychiatric conditions including depression. There are findings suggesting that these drugs might have genotoxic, carcinogenic, and/or mutagenic effects. Therefore, the present in vitro study is intended to investigate potential genotoxic and cytotoxic effects of the antidepressants escitalopram (selective serotonin reuptake inhibitor) and doxepin (Tricyclic antidepressant) on human peripheral lymphocytes cytokinesis-block micronucleus (CBMN), sister chromatid exchange (SCE), and single cell gel electrophoresis (alkaline comet assay) were used for the purpose of the study. In the study, four different concentrations of both drugs (1, 2.5, 5, and 10 µg/mL) were administered to human peripheral lymphocytes for 24 h. The tested concentrations of both drugs were found to exhibit no cytotoxic and mitotic inhibitory effects. SCE increase caused by 5 and 10 µg/mL of escitalopram was found statistically significant, while no statistically significant increase was observed in DNA damage and micronucleus (MN) formation. Moreover, the increase caused by doxepin in MN formation was not found statistically significant. Besides, 10 µg/mL of doxepin was demonstrated to significantly increase arbitrary unit and SCE formation. These findings suggest that the investigated concentrations of escitalopram and doxepin were non-cytotoxic but potentially genotoxic at higher concentrations.