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AbstractPurposeMaterials and methodsResultsConclusionsDetermination of the value of relative biological effectiveness (RBE) of heavy charged ions in vivo is an important task for their optimal use in particle radiotherapy. The aim of this study was to determine the RBE value of a beam of carbon ions with an energy of 450 MeV/nucleon in different regions of the Bragg curve in irradiation of mice at low, medium, and high doses in comparison with X-ray radiation.SHK mice (n = 330) were irradiated in three regions of the Bragg curve in the dose range of 0–1.5 Gy for cytogenetic damage detection and at a dose of 6.5 Gy for determination of 30-day survival. For irradiation of mice in the Bragg peak, two widths of a spread-out Bragg peak (SOBP) were used: 10 mm (LET ∼100 keV/µm) and 30 mm (LET ∼39 keV/µm).The RBE value was 0.8–0.9 before the Bragg peak (LET ∼15 keV/µm) and 0.8 after the peak (LET ∼5 keV/µm), and did not depend on the determination method, despite the differences in LET values. The RBE value determined by the micronucleus test was 1.1–1.7 for the 10-mm-wide SOBP and 1.0–1.3 for the 30-mm-wide SOBP, with the highest RBE value obtained in the low-dose region upon irradiation of mice in the 10-mm-wide Bragg peak. The RBE values in the high-dose region determined by the 30-day survival test lay in the range from 1.4 to 2.6 depending on the width of the Bragg peak and the chosen criterion for calculating the value. The RBE values in the 10-mm-wide Bragg peak (LET ∼100 keV/µm) were higher than those in the 30-mm-wide Bragg peak (LET ∼39 keV/µm) at all used criteria.The present findings suggest that there is the complex relationship between LET and organism response to accelerated charged particle radiation, and the contribution of specific factors and mechanisms must be further considered. [ABSTRACT FROM AUTHOR]

Although the last pandemic created an urgency for development of vaccines, there was a continuous and concerted effort to search for therapeutic medications among existing drugs with different indications. One of the medications of interest that underwent this change was infliximab (IFM). This drug is used as an anti-inflammatory, predominantly in patients with Crohn 's disease, colitis ulcerative, and rheumatoid arthritis. In addition to these patients, individuals infected with Coronavirus Disease (COVID-19) were administered this chimeric monoclonal antibody (IMF) to act as an immunomodulator for patients in the absence of comprehensive research. Consequently, the present study aimed to examine the genotoxic effects attributed to IFM treatment employing different assays in vivo using mouse Mus musculus. Therefore, IFM was found to induce genotoxic effects as evidenced by the comet assay but did not demonstrate genotoxic potential utilizing mouse bone marrow MN test. The results of evaluating the expression of the P53 and BCL-2 genes using RT-qPCR showed stimulation of expression of these genes at 24 hr followed by a decline at 48 hr. Although the comet assay provided positive results, it is noteworthy that based upon negative findings in the micronucleus test, the data did not demonstrate significant changes in the genetic material that might affect the therapeutic use of IFM. The stimulation of expression of P53 and BCL-2 genes at 24 hr followed by a decline at 48 hr suggest a transient, if any, effect on genetic material. However, there is still a need for more research to more comprehensively understand the genotoxic profile of this medication. [ABSTRACT FROM AUTHOR]

• Psidium fruits showed antioxidant activities, with a protective effect on DNA. • It may be related to phenolic compounds, flavonoids, tannins and anthocyanins. • Its fruits had no cytotoxicity, except for the P. myrtoides highest concentrations. • Aqueous extracts of Psidium fruits showed no genotoxic effects. • Psidium fruits are potential sources for functional foods, with benefits for health. Psidium cattleianum Sabine and P. myrtoides O. Berg (Myrtaceae) fruits, known as yellow and purple araçá, respectively, are widely consumed fresh and are used in several applications, such as juices, syrups, and ice cream products. Moreover, their extracts and essential oils have been recognized for their biological properties. Here, we evaluated the potential of P. cattleianum and P. myrtoides fruits through antioxidant, cytogenotoxic, and antigenotoxic tests using their aqueous fruit extracts (1.56 to 50.0 mg/mL). Phenolic compounds and flavonoids were present in both Psidium fruit extracts, while tannins and anthocyanins were found only in P. myrtoides. The latter species exhibited higher antioxidant activity when compared to P. cattleianum according to the DPPH and ABTS tests. Psidium cattleianum extracts showed no cytotoxicity (MTT assay), while P. myrtoides was considered cytotoxic only at the highest concentrations (25 and 50 mg/mL). No genotoxic effects were observed for both extracts (3.12, 6.25, and 12.5 mg/mL) using micronucleus test with the fibroblast cell line L929. Additionally, P. cattleianum and P. myrtoides extracts (12.5 mg/mL) reduced nuclear changes induced by MMS in the antigenotoxic assay. Overall, our findings suggest that the analyzed Psidium fruits, particularly the P. myrtoides species, are sources of natural antioxidants, with no genotoxicity (≤ 12.5 mg/mL) and exhibit a protective effect against DNA damage. [ABSTRACT FROM AUTHOR]

Haematological and genotoxicological parameters of the Levant green frog Pelophylax bedriagae (Camerano, 1882) and the Western Caspian turtle Mauremys rivulata (Valenciennes, 1833) were studied. These species inhabited two sites with differing water quality in the Sarıçay Stream passing through the city centre of Çanakkale, Türkiye. We examined whether the two species were affected by the water quality classes identified based on physical and chemical properties of the water. Statistically significant differences were found between the two sites in terms of the frequencies of micronucleus, lobbed, notched, kidney-shaped and blebbed nuclei, as well as total nuclear abnormality in Pelophylax bedriagae. Moreover, a higher rate of nuclear abnormalities was observed at the more polluted site, classified as water quality class IV. Statistically significant differences were observed in the haematocrit value, percentages of lymphocytes, eosinophils, heterophils and basophils, erythrocyte width and frequencies of lobbed and kidney-shaped nuclei as well as the heterophil/lymphocyte ratio, often used as a stress indicator, in Mauremys rivulata. In this species, it was determined that parameters other than lymphocyte and eosinophil percentages were higher in specimens from the more polluted site. [ABSTRACT FROM AUTHOR]

Rubus imperialis Chum. Schl. (Rosaceae) have demonstrated some pharmacological activities, including gastroprotective action. However, genotoxic effects of R. imperialis extract was also reported. Since niga‐ichigoside F1 (NIF1) is a major compound of this plant species, and which has proven pharmacological properties, it is essential to investigate whether this compound is responsible for the observed toxicity. Therefore, the objective of this study was to analyze the effects of NIF1 on HepG2/C3A cells for possible cytogenotoxicity, cell cycle and apoptosis influence, and expression of genes linked to the DNA damage, cell cycle, cell death, and xenobiotic metabolism. The results showed no cytogenotoxic effects of NIF1 at concentrations between 0.1 and 20 μg/ml. Flow cytometry also showed no cell cycle or apoptosis disturbance. In the gene expression analysis, none of the seven genes investigated showed altered expression. The data indicate that NIF1 has no cytogenotoxic effects, and no interruption of the cell cycle, or induction of apoptosis, apparently not being responsible for the cytotoxic effects observed in the crude extract of R. imperialis. Niga‐ichigoside F1 (NIF1) is a major compound of Rubus imperialis plant and has proven pharmacological properties. This study aimed to analyze the effects of NIF1 on HepG2/C3A cells for possible cytogenotoxicity. The results showed no genotoxic effects by the comet assay and no clastogenic/aneugenic effects by the micronucleus test at concentrations between 0.1 and 20 μg/ml. Flow cytometry also showed no cell cycle or apoptosis disturbance. None of the seven genes involved with this metabolic pathways showed altered expression. [ABSTRACT FROM AUTHOR]

Objectives: To determine the genetic effects of panoramic radiography on the epithelial cells of the buccal mucosa by examining the micronucleus formation in these cells. Materials and Methods: In this cross‐sectional study, exfoliative cytology samples were prepared from the buccal mucosa of 36 patients immediately before and 10 days after panoramic radiography. The samples were prepared using liquid‐based cytology with Papanicolaou staining. The slides were simultaneously evaluated by two expert pathologists and the ratio of the number of cells with micronuclei to the total number of cells on the slide was reported as a percentage. Data analysis was done using paired‐samples T test, Pearson's correlation coefficient, and covariance analysis (α = 0.05). Results: The study sample consisted of 24 (66.67%) males and 12 females (33.33%) with a mean (SD) age of 27.36 (8.19) years. The frequency of cells with micronucleus before and after panoramic radiography was not statistically different (p = 0.468). Additionally, the frequency of micronucleated cells was not correlated with age (p = 0.737) and sex (p = 0.211). Conclusion: Panoramic exposure slightly increased the frequency of cells with micronucleus in epithelial cells of the buccal mucosa. However, this increase was not statistically significant. [ABSTRACT FROM AUTHOR]

The present study was designed to investigate the cytotoxic effects and bioaccumulation of heavy metals iron (Fe), zinc (Zn), copper (Cu), cadmium (Cd), lead (Pb), manganese (Mn), nickel (Ni), and chromium (Cr) in different parts (muscle, gills, and liver) of Tilapia zillii occurring in polluted drainage canal and fish farm, which is located in Abiece region in front of village number 10, Alexandria governorate, Egypt. Results of water analysis revealed the concentration of Cd, Pb, Mn, Ni, and Cr exceeded the limits defined by the American Public Health Association (APHA) in the polluted drainage canal. In addition, the concentration of Ni elevated to the standard limits of APHA and Cu was not detected in the fish farm. Different types of chromosomal aberrations were recorded (e.g., stickiness, fragmented chromosomes, centromeric gaps, chromatid break, chromatid deletion, and tetraploid). Micronucleus frequency was found to be 5.58 in the polluted drainage canal group and 0.32 in the fish farm group. Other nuclear abnormalities such as blebbed nucleus, segmented nucleus, enucleated erythrocyte, kidney-shaped nucleus, heart-shaped nucleus, polymorphic irregular nuclei, binucleated cell, nuclear fragmented erythrocyte, long nucleus, putative fragmented notched nucleus, lobed nuclei, fused erythrocytes, necrotic erythrocyte, and vacuolated nucleus were recorded. The total of erythrocytes nuclear morphological abnormalities was 70.33% in the polluted drainage canal and 1.78% in the fish farm. [ABSTRACT FROM AUTHOR]

The Grass Snake (Natrix natrix) and the Dice Snake (Natrix tessellata) are potential bioindicator water snake species in certain aquatic habitats. The aim of this study is to evaluate the frequency of erythrocytic abnormalities, immature erythrocyte index, and nuclear abnormalities in Natrix natrix and Natrix tessellata from Biga Stream in Çanakkale, Türkiye. Erythrocytic abnormalities and nuclear abnormalities such as micronuclei, lobbed nuclei, notched nuclei, blebbed nuclei, and binucleate cells were observed in peripheral blood smears for each sample. According to our results, total erythrocytic abnormalities in N. natrix (3.01±0.55%) were higher than in N. tessellata (2.52±0.32%). Similarly, the frequency of total nuclear abnormalities in N. natrix (13.40±2.7%) was higher than in N. tessellata (12.68±5.81%) but there was no statistically significant difference in total erythrocytic and nuclear abnormalities. However, student's t-test revealed that there was a statistically significant difference between the two species only in terms of immature erythrocyte index (p: 0.008) which was higher in N. natrix. Due to the results, it was suggested that N. natrix may exhibit more physiological responses to envirenmental stress factors. [ABSTRACT FROM AUTHOR]

The present study aimed to report the morphometric and hematological indices and genotoxicity of a free-life population of D'Orbigny's slider turtles (Trachemys dorbigni) living in an urban area in Southern Brazil. For that, 16 specimens were randomly captured in an urban canal that receives irregular releases of wastewater. Biometrics and external visual changes were analyzed, such as turtle shell deformities, and the presence of parasites. Blood samples were collected to evaluate the hematological profile and the presence of micronuclei and other erythrocyte nuclear abnormalities as potential mutagenic and genotoxic effects. Water physicochemical parameters were also measured. Organisms with ectoparasites (31.25%) and small carapace deformations (56.25%) were observed, but maximum carapace length and weight were considered normal for the species according to the literature. The blood profile indicated low hemoglobin and hematocrit and a high number of total leukocytes, particularly eosinophils which characterize parasitic infections. A frequency of 0.12% for the micronucleus was considered basal, but the frequency of other erythrocyte abnormalities was evident, mainly of blebbed nuclei (63.79%), indicating chromosomal damage in the early stage. The results of this study suggest that natural populations of chelonian inhabiting urbanized areas are impacted by anthropogenic activities in the surrounding environment. Furthermore, it provides comprehensive data which can serve as a comparative model for environmental monitoring studies involving turtles. [ABSTRACT FROM AUTHOR]

Vigabatrin (VGB) is a gammaaminobutyric acid-ergic (GABA-ergic) antiepileptic drug (AED) and is one of 2 approved drugs available to treat infantile spasms (IS). The aim of this study is to elucidate conflicting data on the toxic effects of VGB and to obtain detailed information about its possible cytogenotoxic effects in human lymphocytes. For this purpose, in vitro Chromosomal Aberration (CA), Sister Chromatid Exchange (SCE), Micronucleus (MN) tests, and Comet Assay were performed to determine possible genotoxic and cytotoxic effects of VGB. In addition, the binding energy level of VGB to DNA was determined in silico by molecular docking. The highest concentration (80 μg/ml) of VGB increased the SCE, CA, MN and micronucleated binuclear cell (BNMN) frequency significantly compared to the control after 24 and 48 hours of treatment. In the tail density and tail length parameters, the dose-dependent increase was found to be statistically significant compared to the control. At the 40 and 80 μg/ml concentrations of VGB for 48 hours caused a statistically significant increase in both CA/Cell and AC percentages, while MI and NDI decreased only significantly at the highest concentration (80 µg/ml) causing. In the Comet Assay head density, tail density and tail length parameters, the dose-dependent increase was found to be statistically significant compared to the control. Also, the in silico molecular docking analysis showed that VGB interacts with B-DNA close to the threshold binding energy. The lowest negative free binding energy (ΔG binding) was found as −5.13 kcal/mol. In conclusion, all results are evaluated together, it has been determined that VGB has cytogenotoxic effects in vitro and binds to DNA in silico with significant free binding energy. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives To determine the genetic effects of panoramic radiography on the epithelial cells of the buccal mucosa by examining the micronucleus formation in these cells. Materials and Methods In this cross‐sectional study, exfoliative cytology samples were prepared from the buccal mucosa of 36 patients immediately before and 10 days after panoramic radiography. The samples were prepared using liquid‐based cytology with Papanicolaou staining. The slides were simultaneously evaluated by two expert pathologists and the ratio of the number of cells with micronuclei to the total number of cells on the slide was reported as a percentage. Data analysis was done using paired‐samples T test, Pearson's correlation coefficient, and covariance analysis (α = 0.05). Results The study sample consisted of 24 (66.67%) males and 12 females (33.33%) with a mean (SD) age of 27.36 (8.19) years. The frequency of cells with micronucleus before and after panoramic radiography was not statistically different (p = 0.468). Additionally, the frequency of micronucleated cells was not correlated with age (p = 0.737) and sex (p = 0.211). Conclusion Panoramic exposure slightly increased the frequency of cells with micronucleus in epithelial cells of the buccal mucosa. However, this increase was not statistically significant.

Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg−1 ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg−1; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg−1) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg−1 and 21.90 mg·kg−1, and those of male mice were calculated to be 58.62 mg·kg−1 and 54.31 mg·kg−1, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg−1 and 11.99 mg·kg−1 for female mice, and 16.28 mg·kg−1 and 10.47 mg·kg−1 for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg−1 and 19.92 mg·kg−1 for female mice, and 24.74 mg·kg−1 and 14.08 mg·kg−1 for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg−1, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.

Methylcarbamate (MC), a reaction product between dimethyl dicarbonate and ammonia or ammonium ion, is a potent hepatocarcinogen in F344 rats. Various genotoxicity tests have shown negative results for MC. Although previous studies have described the effects of MC on the liver, including the formation of characteristic basophilic cytoplasmic inclusions (CIs) in hepatocytes, the toxicological significance of CIs and their involvement in hepatocarcinogenesis remain unclear. In the current study, to elucidate the mechanisms of MC hepatocarcinogenesis, we examined hepatotoxicity and genotoxicity after 4 weeks of administration of MC using gpt delta rats with an F344 genetic background as a reporter gene transgenic animal model. Histopathologically, single-cell necrosis, karyomegaly, and the formation of CIs positive for Feulgen staining were observed in hepatocytes at the carcinogenic dose, demonstrating the hepatotoxicity of MC. CIs were also detected as large micronuclei in liver micronucleus tests but not in the bone marrow, suggesting that MC could cause chromosomal instability specifically in the livers of rats. Reporter gene mutation assays demonstrated that MC did not induce mutagenicity even in the liver. Immunofluorescence analyses revealed that CIs exhibited loss of nuclear envelope integrity, increased heterochromatinization, and accumulation of DNA damage. An increase in liver STING protein levels suggested an effect on the cyclic GMP-AMP synthase/stimulator of interferon genes innate immune pathway. Overall, these data demonstrated the possible occurrence of chromothripsis-like chromosomal rearrangements via CIs. Thus, the formation of CIs could be a crucial event in the early stage of MC-induced hepatocarcinogenesis in F344 rats. [ABSTRACT FROM AUTHOR]

Objective: is to assess parameters of cytokine profile, and some biomarkers of hemogram, cytogenetic damage, and oxidative stress to determine their associations with clinical symptoms and identify early prognostic factors for tick-borne encephalitis febrile form compared with Lyme borreliosis non-erythemal form at the onset of the disease.Materials and methods. In 25 patients with febrile tickborne encephalitis (mean age: 49.51 years), 24 patients with Lyme borreliosis non-erythemal form (mean age: 46.70 years) and 14 healthy donors (mean age: 47.20 years), the following parameters were analyzed: hemogram, blood leukocyte indices, cytokine profile, the levels of micronucleated T-lymphocytes, malondialdehyde and total immunoglobulin (Ig) G. For statistical analysis, the Mann–Whitney U-test, Pearson’s goodness-of-fit test, Spearman’s correlation coefficient, and ROC assay with AUC assessment were used.Results. In the tick-borne encephalitis patient group compared to the controls, the following parameters were increased: neutrophil count, blood leukocyte indices, the levels of micronucleated T-lymphocytes, malondialdehyde and proinflammatory cytokines in the blood, which directly correlated with maximal pyrexia levels. Prognostic value for early preliminary diagnosis of tick-borne encephalitis compared with borreliosis showed the following blood parameters: increases in neutrophil count and the levels of micronucleated T-cells, neutrophils to monocytes ratio, neutrophils to lymphocytes ratio, concentrations of malondialdehyde, tumor necrosis factor (TNF)-α, interleukins (IL)-8, IL-6, IL-10, and TNF-α/IL-4 ratio as well as decreases in the levels of IL-4 and total serum IgG. The parameters showed from average to excellent predictive ability as well as high positive and negative predictive values.Conclusion. In patients with tick-borne encephalitis, we detected correlations between the pyrexia levels and the biomarkers of inflammation, oxidative stress, and cytogenetic damage as well as it were found some differences in these parameters from the group of borreliosis patients, which probably had prognostic significance.

ABSTRACT The aim of this article is to identify and evaluate the genomic stability of visceral leishmaniasis in naturally infected dogs. A total of 32 dogs participated in the study, 24 of which were asymptomatic animals, naturally infected, and 8 uninfected, used as a control group. The comet and micronucleus assay tests were performed on bone marrow cells obtained by means of aspiration puncture. For data analysis, the Shapiro-Wilk test was used to verify the normality of the data, and then the Mann-Whitney and T-tests for the comparison between the infected and control groups. The analysis of samples from naturally infected animals and healthy animals showed that the infection caused by the protozoan responsible for leishmaniasis was not able to induce DNA damage in the cells of the infected animals. In the results obtained through the micronucleus test, an increase in the number of micronuclei were observed in polychromatophilic erythrocytes in the medullary tissue of the infected group, when compared to the control group. As a main contribution, the results expressed in this study, consider that the comet and micronucleus assays are suitable for the biomonitoring of genomic stability in bone marrow cells of naturally infected dogs with visceral leishmaniasis.

Introduction and objective: Exclusive breastfeeding (EB) and adequate complementary feeding stand out among the dietary practices for promoting maternal and child health. Thus, this study evaluated the relationship between dietary practices, infant and gestational nutritional status, maternal education, and DNA damage in children from a city in the interior of southern Brazil. Material and methods: Cross-sectional study was carried out with children aged between 6 and 24 months who attended a Family Health Strategy in the city of Passo do Sobrado/RS. The child's diet and level of DNA damage were analyzed. Also, the child's nutritional status and the mother's gestational status were classified, as well as maternal education. Results: Of the 31 children evaluated, there was a low prevalence of EB (29%), which was associated with the early introduction of salty porridge (p=0.002) and food sources of sugar (p=0.017). Although 58.1% of children were at risk for overweight and overweight/obesity, there was no association with EB duration (p=0.735). Furthermore, it was found that 45.2% of the mothers were overweight and obese for their gestational age, which was not associated with the children's current nutritional status (p=0.235). As for DNA damage, a significantly higher frequency of cells with micronuclei (p=0.024) was observed in children who received EB between 2-3 months compared to EB up to the sixth month. Conclusion: There was a prevalence of EBF up to six months of age, associated with the early introduction of foods and high consumption of foods not recommended in this age group, as well as DNA damage. [ABSTRACT FROM AUTHOR]

Hydroxycoumarins are an important source of biologically active compounds. Previous studies have shown that the number and position of the hydroxyl substituents in the scaffold play an important role for the observed biological activity. In the present study, 3-(3-hydroxyphenyl)-7-hydroxycoumarin was synthesized, and potential cytogenotoxic effects determined in human HepG2/C3A cells displaying phase 1 and phase 2 enzymes (metabolizing cell ability) and compared to human peripheral blood mononuclear cells (PBMC) without xenobiotics metabolizing capacity. Cell viability was determined with concentrations between 0.01 and 10 µg/ml of 3-(3-hydroxyphenyl)-7-hydroxycoumarin using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) and trypan blue tests. Genotoxicity was determined utilizing the comet assay, and the clastogenic/aneugenic potential employing the micronucleus (MN) test. The results of the in vitro cytotoxicity assays showed a significant decrease in cell viability of PBMC following exposure to 10 µg/ml concentration of the studied compound after 48 and 72 hr. Comet assay observations noted significant DNA damage in PBMC after 4 hr treatment. No marked cytogenotoxic effects were found in HepG2/C3A cells. No chromosomal mutations were observed in both cell lines. It is important to note that 3-(3-hydroxyphenyl)-7-hydroxycoumarin may exert beneficial pharmacological actions at the low micromolar range and with half-life less than 24 hr. Therefore, the results obtained encourage the continuation of studies on this new molecule for medicinal purposes, but its potential toxicity at higher concentrations and longer exposure times needs to be investigated in further studies. [ABSTRACT FROM AUTHOR]

Urban activities pollute aquatic ecosystems, and the integrity of organisms such as fish. The use of cytological techniques, such as the analysis of blood cellular integrity using the Micronucleus test, can help detect mutagenic damage as a result to urban effluents exposure. In this context, this study aimed to evaluate the frequency of micronucleus and other nuclear abnormalities in Oreochromis niloticus fish environmentally exposed to urban effluents in relation to their erythrocyte recovery capacity when exposed to clean water (30 and 45 days). The results indicated high copper, dissolved iron, nickel, and thermotolerant coliform levels in the urban stream. There was no difference in the frequency of micronuclei. In contrast, cells with nuclear nuclei, binucleates, kidney-shaped nuclei, notched nuclei, lobed nuclei, and segmented nuclei decreased according to the time the fish were exposed to clean water. When exposed to clean water, we conclude that urban fish recover from genotoxic and cytotoxic damage. [ABSTRACT FROM AUTHOR]

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Oenothein B (OeB) is a dimeric ellagitannin with potent antioxidative, antitumor, immunomodulatory, and anti-inflammatory properties. Despite the promising activities of OeB, studies examining the genotoxic or protective effects of this ellagitannin on DNA are scarce. Therefore, to further comprehensively elucidate the chemopreventive profile of OeB, the aim of this study was to evaluate the mutagenic and antimutagenic actions of OeB using Salmonella typhimurium strains with the Ames test. The micronucleus (MN) test and comet assay were used to assess the anticytotoxic and antigenotoxic effects of OeB on mouse bone marrow cells following differing treatments (pre-, co-, and post-treatment) in response to cyclophosphamide (CPA)-induced DNA damage. In addition, histopathological analyses were performed to assess liver and kidney tissues of Swiss Webster treated mice. Our results did not detect mutagenic or antimutagenic activity attributed to OeB at any concentration in the Ames test. Regarding the MN test, data showed that this ellagitannin exerted antigenotoxic and anticytotoxic effects against CPA-induced DNA damage under all treatment conditions. However, no anticytotoxic action was observed in MN test after pre-treatment with the highest doses of OeB. In addition, OeB demonstrated antigenotoxic effects in the comet assay for all treatments. Histopathological analyses indicated that OeB attenuated the toxic effects of CPA in mouse liver and kidneys. These findings suggest that OeB exerted a chemoprotective effect following pre- and co-treatments and a DNA repair action in post-treatment experiments. Our findings indicate that OeB protects DNA against CPA-induced damaging agents and induces post-damage DNA repair. [ABSTRACT FROM AUTHOR]

Background. Chloramine-T (CL-T) is a synthetic sodium salt used as a disinfectant in fish farms to combat bacterial infections in fish gills and skin. While its efficacy in pathogen control is well-established, its reactivity with various functional groups has raised concerns. However, limited research exists on the toxicity of disinfection by-products to aquatic organisms. Therefore, this study aims to assess the sublethal effects of CL-T on adult zebrafish by examining biomarkers of nucleus cytotoxicity and genotoxicity, acetylcholinesterase (AChE) inhibition, and histopathological changes. Methods. Male and female adult zebrafish (wildtype AB lineage) specimens were exposed to 70, 140, and 200 mg/L of CL-T and evaluated after 96 h. Cytotoxic and genotoxic effects were evaluated by estimating the frequencies of nuclear abnormalities (NA), micronuclei (MN), and integrated optical density (IOD) of nuclear erythrocytes. Histopathological changes in the gills and liver were assessed using the degree of tissue changes (DTC). AChE activity was measured in brain samples. Results and conclusions. At a concentration of 200 mg/L, NA increased, indicating the cytogenotoxic potential of CL-T in adult zebrafish. Morphological alterations in the nuclei were observed at both 70 and 200 mg/L concentrations. Distinct IOD profiles were identified across the three concentrations. There were no changes in AChE activity in adult zebrafish. The DTC scores were high in all concentrations, and histological alterations suggested low to moderate toxicity of CL-T for adult zebrafish. [ABSTRACT FROM AUTHOR]

Two different drug groups, typical (classic) and atypical (new), are used in the treatment of schizophrenia. Aripiprazole, an atypical antipsychotic chemical, is the active ingredient of the drug Abilify. This study was conducted to determine the possible genotoxic effect of aripiprazole. For this purpose, four different doses of aripiprazole (5; 10; 20, and 40 µg/mL) were examined with Chromosome Abnormality (CA), Sister Chromatid Exchange (SCE), Micronucleus (MN) tests. Based on these tests, Proliferation Index (PI), Percent Abnormal Cells (AC), Mitotic Index (MI), Micronuclear Binuclear Cell (MNBN), and Nuclear Division Index (NDI) levels were determined in human peripheral lymphocytes treated for 24 and 48 hours. Also, to determine possible binding sites of Aripiprazole on B-DNA molecular docking analysis was performed using AutoDock 4.0 (B-DNA dodecamer, PDB code: 1BNA). Aripiprazole binds to B-DNA with a very significant free binding energy (–11.88 Kcal/mol). According to our study, aripiprazole did not significantly change SCE, CA, AC percentage, MN frequencies when compared with control. According to these results, aripiprazole does not have a genotoxic effect. At the same time, no significant change was observed in the PI, MI, and NDI frequencies when compared with the control. In line with these results, it was observed that the use of aripiprazole in the treatment of schizophrenia did not pose any acute genotoxic and cytotoxic risk. [ABSTRACT FROM AUTHOR]

In this work, we evaluated the subchronic toxicity of FeSe nanoparticles (NPs) in tadpoles of Rana saharica. Tadpoles were exposed for 1–3 weeks to FeSe NPs at 5 mg/L and 100 mg/L rates. Parameters of oxidative stress were measured in whole larvae, and the micronucleus test was performed on circulating blood erythrocytes. We noted a disturbance of the detoxification systems. Enzymatic and non-enzymatic data showed that exposure to FeSe NPs involved a highly significant depletion of GSH, a significant increase in GST activity, and a lipid peroxidation associated with a highly significant increase in MDA. We also noted a neurotoxic effect characterized by a significant inhibition of AChE activity. A micronucleus test showed concentration-dependent DNA damage. This research reveals that these trace elements, in their nanoform, can cause significant neurotoxicity, histopathologic degeneration, cellular and metabolic activity, and genotoxic consequences in Rana larvae. [ABSTRACT FROM AUTHOR]

Sevelamer hydrochloride (SH) and calcium carbonate (CaCO3) are two agents included in the phosphate-binding group which are frequently prescribed in the treatment of patients with hyperphosphatemia. However, there are no satisfactory studies on the genotoxic effects of SH in vitro. This study was conducted to reveal the genotoxic and/or cytotoxic potential of these two drugs in cultured human peripheral lymphocytes. Human peripheral lymphocytes were treated with SH and CaCO3 at sublethal concentrations for 24 or 48 h for micronucleus assay and 1 h in the comet assay. CaCO3 and SH stimulated a slight increase in micronucleus formation however this increase was not significant compared to the control group. According to the findings of the comet test, only one concentration of the SH caused significant DNA damage (2 mg/ml, 48 h) whereas CaCO3 did not cause important DNA breakage. No significant oxidative damage or anti-radical effect caused by test substances was observed on the pure pBR322 plasmid DNA in a cell-free medium. Also, it was found that the drugs were devoid of mutagenic activity in the Ames test, but had a weak cytotoxic effect. Both test substances, particularly SH, significantly reduced the nuclear division index compared to the control group. In conclusion, the cytotoxic effect of SH was evident on the basis of in vitro tests and slightly higher than CaCO3. [ABSTRACT FROM AUTHOR]

The opioid agonist hydromorphone is indicated for the management of severe acute and chronic pain given that alternate treatments are insufficient. While the genotoxicity profile of hydromorphone is well investigated, little is known about the genotoxic potential of its impurities. In this study, 2,2-bishydromorphone was tested in silico and in vitro for both its mutagenic potential in an Ames test performed with Salmonella typhimurium and Escherichia coli tester strains up to a maximum concentration of 5 mg per plate in the absence and presence of metabolic activation. Furthermore, it was tested for its ability to induce micronuclei in TK6 cells in a micronucleus test up to a maximum concentration of 500 µg/mL with or without an exogenous metabolic activation system. 2,2-Bishydromorphone did not reveal any potential for inducing mutagenicity or clastogenicity under the conditions of the respective tests and is therefore considered non-mutagenic and non-clastogenic/aneugenic in vitro. These results are in line with negative in silico quantitative structure-activity relationship (QSAR) prediction for 2,2-bishydromorphone mutagenicity and clastogenicity and provide evidence of good correlation of in silico and in vitro data. Conclusively, these studies add important new clinically relevant information on the safety of hydromorphone as the impurity of 2,2-bishydromorphone is proven to be non-mutagenic and non-clastogenic. [ABSTRACT FROM AUTHOR]

Purpose. To study the genetic peculiarities of pedigree tocksof Amur carp and evaluate its genetic variability by analyzing distribution of alleles and genotypes by the specific protein systems and cytogenetic parameters. Methodology. Analysis of polymorphism of protein systems was performed using electrophoresis in polyacrylamide gel. As protein markers to evaluate the genetic structure of Amur carp stocks, the separation of allelic and genotypic frequencies by loci, which encode a number of fish blood proteins, were used: transferrin (TF), albumin (ALB) and esterase (EST, 3.1.1.1). Cytogenetic analysis was performed using the micronucleus test and analysis of apoptosisfrequencies. Collection and processing of biological material of fish as well as statistical processing of the obtained data was performed using generally accepted methods. Findings. A comprehensive analysis of the genetic structure of Amur carp from three farms in Ukraine was carried out by protein systems and cytogenetic markers. The results of the study showed that all pedigree groups of Amur carp were characterized by a deviation towards the predominance of heterozygotes (Fis = from –0.084 to –0.344). A minimal imbalance was observed in the group of carp from the farm “Karpatskyi Vodogray” LLC (Fis = –0.084). The maximum violation of the genetic balance was found in carp from the farm of JSC “Sumyrybhosp” (Fis = –0.308) and in the group from the experimental farm “Veliky Lyubin” (Fis = –0.344). In general, the analysis of the protein systems of fish blood showed a high level of heterogeneity of pedigree stocks of Amur carp from different farms in Ukraine. The analysis of frequencies of cytogenetic parameters of Amur carp from three fish farms showed that fish from fish farms of JSC “Sumyrybhosp” and PFE “Dzherelo” were characterized by a lower frequency of erythrocytes with micronuclei (EMN) (3.3±0.3 ‰), (3.2±0.3 ‰), lymphocytes with micronuclei (LMN) (2.1±0, 2 ‰), (1.9±0.2 ‰), and apoptosis (4.2±0.3‰), (4,3±0,3‰) compared to the group from fish farm “Karpatskyi Vodogray” LLC, where these values were as follows: EMN (4.7±0.3 ‰), LMN (2.4±0.2‰), apoptosis (5.6±0.4‰). These results indicates a lower level of destabilization of chromosomal apparatus of Amur carp from the fish farm JSC “Sumyrybhosp” at the time of the study. Originality. A comprehensive evaluation of the level of variability of the genetic structure of pedigree stocks of Amur carp from different regions of Ukraine was performed for the first time. Practical Value. Pedigree socksof Amur carp have important practical value in selective breeding work with carps, including works for obtaining hybrid lines to increase the resistance of breeding material.

The aim of this safety study in mice was to determine in vivo toxicity and biodistribution potential of a single and multiple doses of L-glutamic acid-g-p(HEMA) polymeric nanoparticles as a drug delivery system. The single dose did not cause any lethal effect, and its acute oral LD50 was >2.000 mg/kg body weight (bw). Multiple doses (25, 50, or 100 mg/kg bw) given over 28 days resulted in no significant differences in body and relative organ weights compared to control. These results are supported by biochemical and histological findings. Moreover, nanoparticle exposure did not result in statistically significant differences in micronucleus counts in bone marrow cells compared to control. Nanoparticle distribution was time-dependent, and they reached the organs and even bone marrow by hour 6, as established by ex vivo imaging with the IVIS® spectrum imaging system. In conclusion, L-glutamic acid-g-p(HEMA) polymeric nanoparticles appear biocompatible and have a potential use as a drug delivery system.

ObjectiveTo examine perfluorooctanoic acid （PFOA）-induced DNA damage using a combined in vivo and in vitro experiment.MethodsAcellular nuclear DNA damage was used as a model to test the damage induced by exposure to 0.00， 0.13， 0.25， and 0.50 mmol/L PFOA for 1 h. The YAC-1 cell was used as the research model. In the cytotoxicity study， the effects of different dosages on cell activity were determined via CCK-8 assay. The final PFOA concentrations were 0， 1.0×10-8， 1.0×10-7， and 1.0×10-6 mol/L. DNA damage was detected after 3 d of exposure. Rats were gavage with 0， 10， 20， 40 mg/kg·BW PFOA twice. The liver， bone marrow， and peripheral blood of rats were removed 6 h after the last administration. Alkaline and neutral comet assay were performed to measure DNA damage. The micronucleus test was performed to measure bone marrow chromosome breakage.ResultsCompared with the control group， acellular and cell alkaline DNA comet assay result showed that the tail DNA% of acellular nuclear DNA increased significantly in each dose group （P0.05）. The tail DNA% of each dose group in the alkaline comet assay was significantly higher than that of the control group （P0.05）. Compared with the control group， the alkaline and neutral comet assay results showed that the tail DNA% of bone marrow， liver， and peripheral blood cells group showed no DNA breakage in each dose group （P>0.05）. Compared with the control group， the test of bone marrow micronucleus was negative （P>0.05）.ConclusionPFOA can cause DNA single-strand breakage at the subcellular level in vitro， and exposure does not induce DNA and chromosome breakage in rats after oral exposure.

Background Chloramine-T (CL-T) is a synthetic sodium salt used as a disinfectant in fish farms to combat bacterial infections in fish gills and skin. While its efficacy in pathogen control is well-established, its reactivity with various functional groups has raised concerns. However, limited research exists on the toxicity of disinfection by-products to aquatic organisms. Therefore, this study aims to assess the sublethal effects of CL-T on adult zebrafish by examining biomarkers of nucleus cytotoxicity and genotoxicity, acetylcholinesterase (AChE) inhibition, and histopathological changes. Methods Male and female adult zebrafish (wildtype AB lineage) specimens were exposed to 70, 140, and 200 mg/L of CL-T and evaluated after 96 h. Cytotoxic and genotoxic effects were evaluated by estimating the frequencies of nuclear abnormalities (NA), micronuclei (MN), and integrated optical density (IOD) of nuclear erythrocytes. Histopathological changes in the gills and liver were assessed using the degree of tissue changes (DTC). AChE activity was measured in brain samples. Results and conclusions At a concentration of 200 mg/L, NA increased, indicating the cytogenotoxic potential of CL-T in adult zebrafish. Morphological alterations in the nuclei were observed at both 70 and 200 mg/L concentrations. Distinct IOD profiles were identified across the three concentrations. There were no changes in AChE activity in adult zebrafish. The DTC scores were high in all concentrations, and histological alterations suggested low to moderate toxicity of CL-T for adult zebrafish.

Harmful cyanobacterial blooms pose a major threat. Among them, Microcystis aeruginosa has raised serious concerns for human health due to its frequent occurrence. In this study, an ecological floating-bed system consisting of activated carbon fibers, aquatic plants (Ipomoea aquatica Forsskal), animals (Daphnia), and a solar-powered ultrasonic device was designed. The algae-killing efficiency, removal mechanism, and toxicological effects of the floating-bed system on Microcystis aeruginosa were determined under different conditions. The results showed that the average activity of algal cell dehydrogenase (DHA) was reduced by 64.09%, the average malondialdehyde (MDA) content was reduced to 0.125 μmol/L, and the average removal rate of soluble protein was 57.22% under optimal conditions (pH = 7, temperature = 25 °C, dissolved oxygen concentration = 5 mg/L, and hydraulic retention time = 36 h). Scanning electron microscopy (SEM) analysis showed that the structure within the cells of Microcystis aeruginosa was severely damaged after treatment with the solar-powered ultrasonic carbon fiber eco-floating-bed system. Fourier transform infrared (FTIR) spectroscopy analysis showed that the pyrrole ring of chlorophyll-a was degraded. In addition, a tadpole-based micronucleus test and a comet assay were conducted to assess cell viability and DNA damage in water samples treated with the floating-bed system, and the results confirmed that chromosome damage and genotoxicity were significantly reduced. These findings suggest that the floating-bed system is effective in destroying algal cells, leading to massive algal cell death and reducing the risk of secondary contamination. This study provides a new perspective for further research on ecological floating-bed technology, demonstrating its potential practical application in the prevention and control of cyanobacterial blooms. [ABSTRACT FROM AUTHOR]

Objectives: To assess genotoxic and cytotoxic effect of commercially available toothpastes with the different whitening ingredients. Materials and methods: In vivo assessment of cytotoxicity and genotoxicity of whitening toothpastes with different ingredients using a buccal micronucleus cytome assay (BMCyt assay) comprised 199 participants randomly divided into ten groups based on used whitening or control/conventional toothpaste. The exfoliated buccal mucosal cells were collected, stained, and microscopically evaluated at baseline (T0), 30 days (T1), and 60 days (T2) after the beginning of treatment and 30 days after completing treatment (T3). Statistical evaluation was performed by repeated-measures analysis of variance (two-way ANOVA), Tukey's test, and multiple regression analysis. Results: The genotoxic parameters showed no biologically significant changes in any of the observed period for the tested toothpastes, while cytotoxic parameters (number of cells with karyorrhexis and condensed chromatin) showed statistically significant difference (P < 0.05) among evaluation periods for the three peroxide-containing toothpastes. Conclusions: Peroxide-containing whitening toothpastes exhibit an increase in certain cytotoxic parameters only during the application period, which return to control values after the cessation of application. Clinical significance: Whitening toothpastes show no genotoxic effect, while peroxide-containing whitening toothpastes may present significant increase of cytotoxicity (measured by the number of karyorrhexis and condensed chromatin) during the application period. However, these changes observed in clinical conditions cannot be considered significant. Trial registration: ClinicalTrials.gov: NCT04460755. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Industrial Hygiene & Toxicology / Arhiv za Higijenu Rada I Toksikologiju is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cytogenetic studies of Pinus sylvestris seed progeny have been carried out for the first time in the Murmansk region of Russia. Seeds were collected in the territory of 6 district forestries: Zelenoborsky, Kovdorsky, Kandalakshsky, Zasheikovsky, Umbsky and Nickelsky, which were at different distances from large copper-nickel plants. Analysis revealed higher S, Cu, and Ni content in Pinus sylvestris tree seeds from the Zasheikovsky and Nickelsky district forestries. Seeds from the Zelenoborsky district forestry had a higher Cu content (13.6 ± 0.5 mg/kg) compared to other areas. It was found that the frequency of mitotic pathologies in all areas of the study exceeded the level of spontaneous mutation in 5%. The most frequent aberrant cells were registered in the root meristem of seedlings from the Zasheikovsky district forestry, and their proportion averaged 9.4 ± 1.3% of the total number of cells studied at the metaphase and ana-telophase of mitosis stages. In Pinus sylvestris seedlings, micronuclei were noted in the cells at the interphase stage, often varying on average from 0.2 ± 0.1% in plants from the Kandalakshsky district forestry to 0.9 ± 0.3% from the Zasheikovsky district forestry. The data obtained testify to the colossal impact of heavy metals on the living organism cell genetic apparatus. The negative effect from industries, as sources of air pollutants, extends over tens of kilometers. Therefore, regularly monitoring the cytogenetic parameters of bioindicators such as Pinus sylvestris is necessary. [ABSTRACT FROM AUTHOR]

Pollution generated by the mining industry can cause harm to wildlife. This study aimed to evaluate the cytotoxicity, genotoxicity and mutagenicity in bats environmentally exposed to open pit mining. Thus, 62 bats of the following species, Carollia perspicillata, Glossophaga soricina, Phyllostomus hastatus, and Desmodus rotundus exposed to mining activities (ferronickel) were used in the analysis. The animals were obtained in samplings in July and November of 2021, totaling 8 days of sampling in the field. The results indicated that species differ in the frequency of genotoxic damage between sampling points within the mining landscape. Cytotoxicity was observed by scoring of karyorrhexis, pyknosis and karyolysis. The most captured species, C. perspicillata, showed differences in DNA damage between exposed and unexposed populations, but no differences were observed between males (n = 14) and females (n = 20). G. soricina was also a sensitive species for indicating a high frequency of DNA damages compared to the omnivore P. hastatus. Elements such as Mn, Cr, Pb, and Zn observed in water samples were at high levels in the mining area. We conclude that bats in mining areas are susceptible to increased DNA damage as already identified for other species. [ABSTRACT FROM AUTHOR]

Abstract Background The use of organotypic human tissue models in genotoxicity has increased as an alternative to animal testing. Genotoxicity is generally examined using a battery of in vitro assays such as Ames and micronucleus (MN) tests that cover gene mutations and structural and numerical chromosome aberrations. At the 7th International Workshop on Genotoxicity Testing, working group members agreed that the skin models have reached an advanced stage of maturity, while further efforts in liver and airway models are needed [Pfuhler et al., Mutat. Res. 850–851 (2020) 503135]. Organotypic human airway model is composed of fully differentiated and functional respiratory epithelium. However, because cell proliferation in organotypic airway models is thought to be less active, assessing their MN-inducing potential is an issue, even in the cytokinesis-blocking approach using cytochalasin B (CB) [Wang et al., Environ. Mol. Mutagen. 62 (2021) 306–318]. Here, we developed a MN test using EpiAirway™ in which epidermal growth factor (EGF) was included as a stimulant of cell division. Results By incubating EpiAirway™ tissue with medium containing various concentrations of CB, we found that the percentage of binucleated cells (%BNCs) almost plateaued at 3 μg/mL CB for 72 h incubation. Additionally, we confirmed that EGF stimulation with CB incubation produced an additional increase in %BNCs with a peak at 5 ng/mL EGF. Transepithelial electrical resistance measurement and tissue histology revealed that CB incubation caused the reduced barrier integrity and cyst formation in EpiAirway™. Adenylate kinase assay confirmed that the cytotoxicity increased with each day of culture in the CB incubation period with EGF stimulation. These results indicated that chemical treatment should be conducted prior to CB incubation. Under these experimental conditions, it was confirmed that the frequency of micronucleated cells was dose-dependently increased by apical applications of two clastogens, mitomycin C and methyl methanesulfonate, and an aneugen, colchicine, at the subcytotoxic concentrations assessed in %BNCs. Conclusions Well-studied genotoxicants demonstrated capability in an organotypic human airway model as a MN test system. For further utilization, investigations of aerosol exposure, repeating exposure protocol, and metabolic activation are required.

Since, fish is a significant native species of the aquatic environment and are exposed to multiple pollution states, they are used as models for ecotoxicological investigations of aquatic contaminants, particularly metal toxicity. We investigated genotoxicity induced in whole blood and gill tissues through comet assay and micronucleus (MN) test in Labeo rohita after 96-hour in vivo static exposure to copper oxide nanomaterials at three sublethal (SL) test concentrations, including sublethal concentration I (SL-I; 1/4th of LC50 = 29.5 µg/liter), sublethal concentration II (SL-II; 1/2nd of LC 50 = 59 µg/liter) and sublethal concentration III (SL-III; 3/4th of LC50 = 88.5 µg/liter), along with a control. The 96-hour LC50 value for copper oxide nanomaterials was estimated to be 118.7 µg/L in a static system in the test species. Tissue samples were collected at 24, 48, 72 and 96 hours postexposure. Results indicated the mean percent DNA damage in the comet tail and MN induction in gills and whole blood showed a concentration-dependent increase up to 96-hour exposure. The results of this investigation will be useful in determining the organ-specific risk of CuO-NM-induced genotoxicity in fish. [ABSTRACT FROM AUTHOR]

Background/Aim: Exposure to chromium (VI) [Cr(VI)] has been postulated to be associated with the induction of cancer. In vivo studies utilizing biomarkers of genotoxic damage could aid in elucidating the mechanisms underlying the genotoxic effects of Cr(VI) and their relationship with carcinogenesis. In this study, the origin (clastogenic and/or aneugenic damage) and kinetics of micronuclei (MN) induced by Cr(VI) were investigated. Materials and Methods: Hsd:ICR female mice were divided into groups of five individuals each. MN kinetics were measured in groups treated with 20 or 25 mg/kg CrO3 intraperitoneally using acridine orange-coated slides in peripheral blood obtained from the caudal vein 0, 12, 24, 36, 48, 60, and 72 h after treatment. Whereas identification of MN with centromeric DNA (MNK+) was measured at the dose of 20 mg/kg of CrO3, using fluorescence in situ hybridization (FISH) with a centromere-specific probe in peripheral blood obtained at 0, 12, and 48 h after treatment. Control groups were administered vehicle only. Results: Total MN were quantified and the clastogenic/aneugenic effects of Cr(VI) were evaluated based on the proportion of MNK+ versus micronuclei without centromeric DNA (MNK-). There was a significant increase in MN frequencies beginning at 12 h in the Cr(VI)-treated groups demonstrating its genotoxicity. When calculating the MNK+ as a percentage of the total MN, the increase was significant beginning 12 h after treatment. Conclusion: The fact that the MNK+ and MNK-were observed at both evaluation times corroborates Cr(VI) as a genotoxic agent and demonstrates that both clastogenic and aneugenic damages are involved in the formation of MN. [ABSTRACT FROM AUTHOR]

Plants with medicinal potential may also produce adverse effects in humans. This seems to be the case for the species Rubus rosifolius, where preliminary studies demonstrated genotoxic effects attributed to extracts obtained from leaves and stems of this plant using on HepG2/C3A human hepatoma cells as a model. Considering the beneficial properties of this plant as an antidiarrheal, analgesic, antimicrobial, and antihypertensive and its effects in the treatment of gastrointestinal diseases, the present study was developed with the aim of determining the cytotoxic and genotoxic potential of extracts of leaves and stems of R. rosifolius in primary without metabolic competence in human peripheral blood mononuclear cells (PBMC). Cell viability analyses at concentrations of between 0.01 and 100 µg/ml of both extracts did not markedly affect cell viability. In contrast, assessment of the genotoxic potential using the comet assay demonstrated significant damage to DNA within PBMC from a concentration of 10 µg/ml in the stem extract, and a clastogenic/aneugenic response without cytokinesis-block proliferation index (CBPI) alterations at concentrations of 10, 20, or 100 µg/ml for both extracts. Under our experimental conditions, the data obtained demonstrated genotoxic and mutagenic effects attributed to extracts from leaves and stems of R. rosifolius in cells in the absence of hepatic metabolism. [ABSTRACT FROM AUTHOR]

Copyright of Environmental & Social Management Journal / Revista de Gestão Social e Ambiental is the property of Environmental & Social Management Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background Genotoxicity in tissues other than hematopoietic tissues, such as the liver and gastrointestinal (GI) tract, is an important focus in the risk assessment of chemicals in humans. We previously developed a rat micronucleus test for the GI tract, which is the first contact tissue where chemicals are introduced into the body through oral exposure. Target cells were obtained from fresh tissue samples by ethylenediaminetetraacetic acid disodium salt (EDTA) treatment. As an improvement to this method, we have used formalin-fixed tissues instead of fresh tissues; this approach can be used for tissues that are sampled from other toxicological tests and that are archived for several years. This new method can be used for examining micronucleus induction retrospectively when needed. In the present study, we compared the performance of the EDTA method and the new method with formalin-fixed tissues (formalin-fixation method). Results Histological examination showed that both the EDTA and formalin-fixation methods could be used for collecting cells located in or above the proliferative zone of the GI tract tissues of rats. In addition, the collected cells were similar in shape. We conducted micronucleus tests with rat GI tract tissues by the two methods using model chemicals, which were used as positive control chemicals (a combination of diethylnitrosamine, 1,2-dimethylhydrazine dihydrochloride, and potassium bromate). The two methods showed similar results. We additionally evaluated the aging effect of tissues stored in formalin fixative. The results showed that 1 year of storage did not affect the frequency of micronucleated cells. Conclusion The equivalence of the EDTA and formalin-fixation methods was confirmed, and micronucleus analysis was possible up to at least 1 year after formalin fixation of the GI tract, indicating that the formalin-fixation method is valuable for the rat GI tract micronucleus test.

Objectives 1-Methylnaphthalene (1-MN) is composed of 2 benzene rings and belongs to polycyclic aromatic hydrocarbons. The metabolism of 1-MN in laboratory animals and bacteria leads to the formation of 1-naphthoic acid (1-NA). Material and Methods In this study the distribution of 1-NA in lung, liver, spleen, kidney and urinary excretion of 1-NA in rats after single and repeated inhalation exposure to 1-MN vapors were investigated. The activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and cytochrome were measured of the rats. Genotoxic effects were evaluated with the in vitro micronucleus test on V79 hamster fibroblasts. Results The concentrations of 1-NA in the tissues of rats after single and repeated exposure to 1-MN were dependent on the exposure dose. High levels of 1-NA were found in kidneys of animals after the single and repeated exposure to 1-MN. With an increase of 1-MN dose, an increase in the activity of cytochrome P450 (CYP1A1 and CYP1A2) was observed in the liver of rats. Compared to control animals, significantly higher ALT activity was noted in serum of rats exposed to 1-MN. The micronuclei frequency in V79 cells exposed to 1-MN (in the range of analyzable concentrations; i.e., 5–25 μg/ml) did not differ significantly from the vehicle control, whereas urine extracts from rats exposed to 1-MN induced a significant increase in the frequency of micronuclei compared to urine extracts from the group of control animals. Conclusions Metabolism of 1-MN in rats after the inhalation exposure leading to 1-NA was mainly observed during the first day after the end of exposure. It is likely that 1-MN metabolites present in rat urine can induce the increased micronuclei frequency as was shown in V79 cells. Int J Occup Med Environ Health. 2022;35(6):731–46

Safety concerns about medical devices playing important role in health sciences and bioengineering research are rising day by day. Although there are specific standards regarding disposable medical materials, the information is updating with the toxicological studies. In this study, cytotoxic/genotoxic effects of chemicals leaking from serum infusion sets that have an important place in the clinic were investigated. Media containing leakage chemicals were prepared from equal samples taken from the plastic line sections of 13 different brands of serum infusion sets containing phthalates and the effects on the cultured cells were compared with the untreated control groups. To obtain leaking chemicals, extracting period was selected as 72 h, a routine set-change time in the clinic as indicated in various publications. Neutral red uptake and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tests were performed in L929 cells to determine cytotoxicity, and cytokinesis blocked micronucleus technique was performed in lymphocytes to determine genotoxicity. Cytotoxic and genotoxic damage levels were compared by evaluating cell-viability rates relative to control, micronucleus frequency, and nuclear division index values. The results showed that all sets caused a decrease in cell viability revealing the effects both on lysosomal and mitochondrial activity and increase in micronucleus frequencies in general. The number of similar studies is extremely limited, and in this study in addition to the short-term effects of using the serum infusion sets, the information about the sample tests to determine the biosecurity of disposable medical materials is given. [ABSTRACT FROM AUTHOR]

3‐(3,4‐Dihydroxyphenyl)‐7,8‐dihydroxycoumarin is a newly synthesized coumarin derivative with a potent antioxidant effect. The aim of the present study is to investigate the safety of this compound, determining the in vitro cytotoxic and genotoxic in human peripheral blood mononuclear cells (PBMC) and in HepG2/C3A cells. Cell viability has been investigated by the trypan blue staining test and MTT assay and the genotoxicity by the comet assay and micronucleus test, using concentrations between 0.01 and 10 μg/ml. The compound proved to be noncytotoxic in both cell lines, at all tested concentrations, protecting the cells from the DNA damage. In addition, this molecule does not show clastogenic/aneugenic effects when performing the micronucleus test with cytokinesis blockade. Based on the obtained data, and the conditions of the experiments, we can conclude that the 3‐(3,4‐dihydroxyphenyl)‐7,8‐dihydroxycoumarin is a safe molecule up to a concentration of 10 μg/ml, which encourages further studies aiming to explore its potential as a drug candidate. 3‐(3,4‐Dihydroxyphenyl)‐7,8‐dihydroxycoumarin is a newly synthesized coumarin derivative with an antioxidant effect. The objective of this study was to investigate the safety of this compound, assessing the in vitro cytotoxicity and genotoxicity. Concentrations between 0.01 and 10 μg/ml proved to be noncytotoxic by the trypan blue staining test and MTT assay. In addition, this molecule does not show genotoxic damage by the comet assay or clastogenic/aneugenic effects when performing the micronucleus test with cytokinesis blockade. [ABSTRACT FROM AUTHOR]

To evaluate the risks of hair dye exposure, we investigated cellular and molecular effects of Arianor Ebony dye, which is a mixture of azo and anthraquinone dyes, used in the composition of the black color. Cytotoxicity, genotoxicity, and gene expression of relevant molecules of apoptotic and oxidative stress mechanisms were investigated in HepG2 cells exposed to Arianor Ebony. Results showed that the dye did not induce cytotoxicity to exposed cells at a concentration up to 50 µg/mL compared to the negative control. However, genotoxic assays indicated that the dye was able to damage the genetic material at a concentration of 25 µg/mL, with induction factor values of exposed cells two- to five-fold higher than those recorded for the negative control. Moreover, the lowest observed effect concentration was 12.5 µg/mL. For gene expression, relevant changes were observed in cytochrome c and caspase 9, which decreased in cells incubated with the dye in a dose-dependent manner when compared with the negative control. In parallel, the expression of genes for antioxidant enzymes was increased in exposed cells, suggesting the presence of metabolic routes that protect cells against the toxic effect of the dye, avoiding exacerbated cellular death. Results suggested that the dye disrupted cellular homeostasis through mitochondrial dysfunction, which may be hazardous to human health. Thus, further investigations are necessary to deeply understand the mechanisms of action of the dye, considering its toxic potential found in our ex vivo assays.

Mesenchymal stromal/stem cells stem (MSC) have been widely studied due to their great potential for application in tissue engineering and regenerative and translational medicine. In MSC-based therapy for human diseases, cell proliferation is required to obtain a large and adequate number of cells to ensure therapeutic efficacy. During in vitro culture, cells are under an artificial environment and manipulative stress that can affect genetic stability. Several regulatory agencies have established guidelines to ensure greater safety in cell-based regenerative and translational medicine, but there is no specific definition about the maximum number of passages that ensure the lowest possible risk in MSC-based regenerative medicine. In this context, the aim of this study was to analyze DNA damage and chromosome alterations in adipose-derived mesenchymal stromal cells (ADMSC) until the eleventh passage and to provide additional subsidies to regulatory agencies related to number of passages in these cells. Thus, two methods in genetic toxicology were adopted: comet assay and micronucleus test. The comet assay results showed an increase in DNA damage from the fifth passage onwards. The micronucleus test showed a statistically significant increase of micronucleus from the seventh passage onwards, indicating a possible mutagenic effect associated with the increase in the number of passages. Based on these results, it is important to emphasize the need to assess genetic toxicology and inclusion of new guidelines by regulatory agencies to guarantee the safety of MSC-based therapies for human diseases.

Cadmium sulfide quantum dots (CdS QDs) are being developed for sensors, fluorescent probes, and other platforms and are attracting increasing attention. Given the growing demand for QDs, it is clear that there is a need to understand their potential toxicity to organisms. However, little is known regarding the genotoxicity of CdS QDs to humans. Therefore, this study used CdS QDs as the research object, cultured human peripheral blood lymphocytes, and randomly divided them into a control group, CdS I group (CdS QDs), and CdS II group (CdS QDs coated with thioglycolic acid). After cultivation, we measured the olive tail distance, tail length, tail DNA%, lymphocyte micronucleus rate, and aneuploid rate. The comet test results indicated that the indices of the QD group were significantly larger than those of the control group (P < 0.05). The results of the micronucleus and chromosome aberration tests showed that the lymphocyte micronucleus rate and chromosome aneuploid rate in the QD group were significantly increased (P < 0.05) compared with those in the control group. In conclusion, CdS QDs have certain genotoxicity to human peripheral blood lymphocytes, and the DNA damage caused by CdS QDs encapsulated with thioglycolic acid is less severe than that caused by nonencapsulated CdS QDs.