Genotoxicity Biomarkers Research Articles

Cytogenetic biomonitoring of road tunnel construction workers: buccal micronucleus cytome assay.

Road tunnel construction workers revealed higher frequencies of cells with genotoxic damage (i.e., MN and NBUD). MN and NBUD resulted to be Poisson distributed and counts of these genotoxicity biomarkers were then analysed by Poisson regression. The frequency ratio (FR) for MN was 1.31 (95% CI: 0.84-2.04), with an increase in the exposed subjects; this finding, though indicating a higher genotoxic risk in the exposed subjects, did not reach statistical significance. On the other hand, the FR for NBUD was 3.49 (95% CI: 1.86-6.56), with a statistically significant increased risk of chromosomal damage. Even the frequencies of binucleated cells (a marker of cell proliferation) and pyknotic cells (a cell death biomarker) were significantly higher in tunnel workers. Tunnel construction workers are exposed to complex mixtures of toxic agents, some of which are known to be genotoxic. The aim of this study was to evaluate the genotoxic risk in this occupational setting by comparing tunnel workers with a control group for frequencies of nuclear aberrations in oral exfoliated cells. To evaluate the genotoxic effects of tunnel air pollutants, we conducted a cross-sectional, molecular epidemiological study (35 tunnel workers and 35 healthy controls) using the buccal micronucleus cytome assay. A questionnaire was administered to obtain information about demographic variables, lifestyle, dietary habits, anthropometric data, and occupational history. Buccal mucosa cells were collected by scraping the buccal mucosa with a small-headed toothbrush. Coded slides were examined blind by trained scorers for micronuclei (MN), nuclear buds (NBUD), and other nuclear abnormalities. Our observations provide further knowledge and understanding of the occupational hazards of tunnel workers and confirm the complexity of effects (cytotoxic and genotoxic) probably induced by fumes and dust produced in underground operations.

Associations of blood lead levels with multiple genotoxic biomarkers among workers in China: A population-based study.

Carcinogenic effects from low doses of lead (Pb) exposure to populations have been suspected but not concluded. Therefore, a large-scale cross-sectional study was conducted by us to investigate genotoxic effects from Pb exposure during 2016-2018 in North China. Blood lead levels (BLLs) and cumulative blood lead levels (CBLLs) were measured. Multiple relevant biomarkers were used to assess genotoxicity of Pb: mitochondrial DNA copy number (mtDNAcn, n=871), Comet Tail Intensity (n=872), γ-H2AX (n=345), relative telomere length (rTL, n=757), micronuclei (MN, n=934) and phosphatidylinositol glycan class A mutation (PIG-A, n=362). The BLL data show right-skewed distribution, with increase of the median (P25, P75) from 17.4 (8.9, 26.4) μg/dl in 2016 to 18.5 (10.5, 27.2) μg/dl in 2017, and to 20.8 (11.3, 31.0) μg/dl in 2018. Multivariate regression analyses show that mtDNAcn was non-linearly associated with BLLs or CBLLs, i.e. decreased at low levels but increased at the higher levels. Comet and Micronuclei data show positive dose-response relationships with BLLs as well as CBLLs. γ-H2AX data show an overall increased trend with BLLs while rTL data show a shortening trend. No associations were found for PIG-A mutation with Pb exposure. Our findings indicate that current low dose exposure to Pb can still cause health hazards to occupational populations, and the mechanism may be via the induction of DNA & chromosome damage rather than via the mutagenesis pathway.

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

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

Genotoxicity, oxidative stress, and biochemical biomarkers of exposure to green synthesized cadmium nanoparticles in Oreochromis niloticus (L.)

The considerable increment in the use of Nanoparticles in the industry has been recognized as an environmental concern today. Therefore, this study aimed to investigate the toxicity effects of green synthesized cadmium nanoparticles [Cd]NPs using Moringa oleifera leaves extract on multi-biomarkers in Oreochromis niloticus after four weeks of exposure. The results showed that LC50 values of [Cd]NPs for 24, 48, 72 and 96 h were 2.17, 1.75, 1.49 and 1.22 mg l−1, respectively. There was a significant decrease in the number of white and red blood cells, hemoglobin, hematocrit, mean corpuscular hemoglobin concentration value in fish exposed to [Cd]NPs. The mean corpuscular volume and neutrophils were increased. [Cd]NPs exposure to fish has led to cytotoxic and genotoxic changes in the erythrocytes. Significant changes were observed in the cortisol, triiodothyronine, and thyroxine levels of the fish exposed to [Cd]NPs. The activities of aspartate aminotransferase and alanine aminotransferase increased. Glucose, total lipids, urea, and creatinine levels increased in the serum of fish exposed to [Cd]NPs, whereas total protein contents and alkaline phosphatase activity decreased. A significant reduction was observed in glycogen, total antioxidant levels, and superoxide dismutase, catalase and glutathione S-transferase activities of fish exposed to [Cd]NPs. In contrast, the [Cd]NPs exposure resulted in a significant increase in DNA fragmentation percentages, lipid peroxidation, and carbonyl protein levels in different tissues. The results of the present study confirmed that [Cd]NPs has the toxicity potential to cause Cyto-genotoxicity, oxidative damages, changes in the hematological and biochemical changes, and endocrine disruptor in the fish.

Multi-biomarker approach and IBR index to evaluate the effects of different contaminants on the ecotoxicological status of Apis mellifera

The honeybee, Apis mellifera L. (Hymenoptera: Apidae), a keystone pollinator of wild plant species and agricultural crops, is disappearing globally due to parasites and diseases, habitat loss, genetic constraints, beekeeper management issues and to the widespread use of pesticides. Besides insecticides, widely studied in this species, honeybees are also exposed to herbicides and fungicides and heavy metals whose lethal and sublethal effects need to be investigated. In this context, our study aimed to evaluate the effects of fungicides and of heavy metals on honeybees and to develop and apply a multi-biomarker approach that include an Integrated Biological Index (IBRv2) to assess the toxicological status of this species. Biomarkers of neurotoxicity (AChE and CaE), metabolic alteration (ALP, and GST) and immune system (LYS, granulocytes) were measured, following honeybees’ exposure to cadmium or to a crop fungicide, using the genotoxic compound EMS as positive control. A biomarker of genotoxicity (NA assay) was developed and applied for the first time in honeybees. At the doses tested, all the contaminants showed sublethal toxicity to the bees, highlighting in particular genotoxic effects. The data collected were analyzed by an IBRv2 index, which integrated the seven biomarkers used in this study. IBRv2 index increased with increasing cadmium or fungicide concentrations. The IBRv2 represents a simple tool for a general description of honeybees ecotoxicological health status. Results highlight the need for more in-depth investigations on the effects of fungicides on non-target organisms, such as honeybees, using sensitive methods for the determination of sublethal effects. This study contributes to the development of a multi-biomarker approach to be used for a more accurate ecotoxicological environmental monitoring of these animals.

Sediment contamination and toxic effects on Violet Goby fish (Gobioides broussonnetii - Gobiidae) from a marine protected area in South Atlantic

The Estuarine-Lagoon Complex of Iguape-Cananéia (ELCIC), a Marine Protected Area (MPA) in Brazil, was the focus of this study that aimed to relate external levels of exposure to contaminants to toxic effects on Gobioides broussonnetii fish. Different anthropogenic contaminants such as metals, polycyclic aromatic hydrocarbons (PAHs) and pharmaceuticals and personal care products (PPCPs) were analyzed in the sediments; and biochemical, histopathological and genotoxicity biomarkers evaluated in fish; in two different seasons at three sites of the estuarine region. Higher contamination of the sediments was observed near the main urban center (Iguape city - IG). Metal concentrations were considered low to moderate, while PAHs concentrations were considered low. The concentrations of PPCPs increased due to the anthropogenic presence and were higher near IG and the Cananéia Island (CI). Contributions from historical mining, agriculture, nautical activities, oil, sewage and waste disposal, biomass and fossil fuels combustion were identified. Higher concentrations of metals and PPCPs were observed during the cold-dry season, suggesting influences of the lower hydrodynamics during the season of lower precipitation. Higher PAHs concentrations occurred in the hot-rainy season, indicating influences of greater human presence in summer. In fish, biological responses followed the same spatial and seasonal pattern. More pronounced changes in antioxidant, biotransformation, histopathological and genotoxic biomarkers were observed in IG and CI. The multivariate analysis and the integrated biomarkers response index (IBR) also evidenced worse environmental conditions in these sites. This result can indicate a negative influence of anthropogenic activities on the contamination of sediments and on the biological responses of fish. This study presented the first ecotoxicological data for the species and suggested that these chronic exposures can cause adverse effects on this fish population. The data contribute to the understanding of local environmental quality and can be applied in the future to the environmental and social management of marine protected areas.

Genotoxic biomarkers in patients on hemodialiasis

It is generally recognized that genotoxic damage have essential etiopathogenetic significance, and its prevention is an important measure to preserve human life and health. In the framework of this concept, literature information on studies of genotoxic biomarkers in patients with various hemodialysis regiments has been reviewed and summarized, and ways to prevent detectable genotoxicity have been identified. Based on the analysis of the known data, it was concluded that patients of this group have an increased level of DNA and chromosome damage in peripheral blood lymphocytes. Based on the results of individual studies, it was shown that one of the strategies for reducing genotoxicity may be the improvement of hemodialysis therapy methods and regimes, as well as pharmacological and nutritional correction of genotoxic effects.

Integrated response of the toxicity of environmentally relevant concentrations of copper in the backwater clam Meretrix casta

ABSTRACT Copper is released into the aquatic environment as a consequence of anthropogenic activities such as mining and runoffs of copper-containing pesticides and fertilisers. This may pose a threat to the health of the organisms inhabiting coastal water bodies or estuaries. The present study was therefore carried out to assess the toxicity of environmentally relevant concentrations of copper in the estuarine backwater clam Meretrix casta. In the experimental setup, clams were exposed to five concentrations of CuCl2 (0.5, 1.0, 1.5, 2.0 and 2.5 μg/L) for 15 days in water. Biomarkers of genotoxicity (Micronucleus test and comet assay), oxidative stress (Catalase and malondialdehyde assays), acetylcholinesterase activity and condition index were employed to study the effects of copper on the clams. Genotoxicity, oxidative stress, acetylcholinesterase activity and condition index were found to be non-significant in all the concentration groups indicating that such low concentrations of copper were unable to induce any toxic response. However, using the Integrated Biomarker Response index, a concentration-dependent increase was observed indicating that the integration of these biomarker responses could give information on early signs of copper contamination in aquatic habitats. Meretrix casta could potentially be used as a sentinel species for monitoring copper contamination in the estuarine environment.

Genotoxic biomarkers in employees of pathomorphological laboratories working with formaldehyde (systematic review)

Introduction. A systematic review and analysis of literature on genotoxic examinations of individuals occupationally exposed to formaldehyde vapors (FAV) when working in pathomorphological laboratories of medical institutions has been performed. Formaldehyde is classified by the WHO International Agency for Research on Cancer as a class I carcinogen. Many studies have been published concerning testification of the genotoxic damage of pathomorphological laboratory personnel working with formaldehyde, identification using various biomonitoring cytogenetic methods, in particular, the micronucleus test in peripheral blood lymphocytes and buccal epithelial cells, a chromosomal aberrations test, and the DNA comet assay.Material and methods. Literature was searched until December 2019 using the MedLine / PubMed database of scientific literature (https://www.ncbi.nlm.nih.gov/PubMed). Key search terms included formaldehyde laboratory micronuclei, formaldehyde laboratory chromosomal aberration, or formaldehyde laboratory DNA comet. Full-text articles published in English in journals with assigned DOIs were considered.Results. All studies reported the presence of FAV in the workplace, while in only half of the cases the level of formaldehyde was not higher than the maximum permissible values. The average exposure to formaldehyde over an 8-hour working day was 0.79 ± 0.43 mg/m3. All studies reported the presence of an increased level of the studied cytogenetic biomarkers compared to controls. A total analysis of the data showed more than a 2.5-fold excess in the level of micronuclei in the peripheral blood lymphocytes of laboratory workers compared with the control groups (8.15 ± 2.57 ‰ vs. 3.56 ± 1.15 ‰; p < 0.05), and more than a 5-fold excess in case of the level of micronuclei in buccal epithelial cells (0.83 ± 0.09 ‰ vs. 0.16 ± 0.01 ‰; p < 0.05).Conclusion. Thus, pathomorphological laboratory personnel exposed to FAV is at potential risk to life and health from the long-term impact of genotoxic eff

Effects of polystyrene nanoplastics on Ctenopharyngodon idella (grass carp) after individual and combined exposure with zinc oxide nanoparticles

The toxicity of polystyrene nanoparticles (PS NPs) and ZnO nanoparticles (ZnO NPs), in combination is poorly known. Thus, the aim of the current study was to evaluate the effects of PS NPs (760 μg/L) on Ctenopharyngodon idella exposed to it, both in separate and in combination with ZnO NPs (760 μg/L), based on behavioral, biochemical and genotoxic biomarkers. Current data have indicated that PS NPs, for a short exposure period (3 days), both in separate and in combination with nanoparticles, have affected animals’ response to the mirror test. On the other hand, all treatments have equally induced C. idella inactivity towards alarm substances and DNA damage. There was increased oxidative stress, mainly in groups exposed to PS NPs (in combination, or not, with nanoparticles); although increased, the evaluated antioxidant levels did not appear to be enough to inhibit the effects of treatment-induced production of free radicals. Together, these results are likely co-responsible for the observed changes. The current study did not observe antagonistic, synergistic or additive effect on animals exposed to the combination between PS NPs and ZnO NPs; however, this outcome should not discourage the performance of similar studies focused on assessing the (eco)toxicity of pollutant mixtures comprising nanomaterials.

Genotoxic effect of heavy metals on Astyanax lacustris in an urban stream

Uncontrolled urbanization growth contributes to the pollution of aquatic environments. Heavy metals released by domestic and industrial effluents can negatively affect aquatic organisms. This study aimed to evaluate the effect of environmental pollutants, such as metals, on fish DNA damage, in stretches of an urban stream. Specimens of the Neotropical fish, Astyanax lacustris, were exposed in situ for 96 h along the Antas stream, a Brazilian aquatic system deteriorated by anthropogenic factors. Water and sediment samples were collected simultaneously for physicochemical and heavy metal analyses. The comet assay was performed as a biomarker of genotoxicity. Fish located downstream had a higher frequency of DNA damage than in the reference site. We found concentrations of Cr and Ni above acceptable levels in sediment samples. Generally, Ba, Mn, Mg, Zn, Cr, and Ni were the elements most associated with genotoxic damage. Water and sediment of the Antas stream showed genotoxic potential in A. lacustris according to the urbanization gradient, demonstrating the importance to prevent the release of environmental pollutants, especially heavy metals in urban areas.

GSTM1 and GSTT1 Null Genotype Polymorphisms and Susceptibility to Arsenic Poisoning: a Meta-analysis.

The value of the glutathione S-transferase (GST) null genotype in patients with arsenic poisoning has been recognized, but the conclusions of previous studies remain inconsistent. The objective of this study was to evaluate the relationship between GST mu 1 (GSTM1) and GST theta 1 (GSTT1) null genotype polymorphisms and susceptibility to arsenic poisoning. PubMed, Medline, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, and WeiPu databases were systematically searched for publications up to March 31, 2020. The quality of the studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. The pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated to estimate the relationship between GSTM1 and GSTT1 null genotype polymorphisms and arsenic poisoning. The meta-analysis was conducted using STATA 14.0 software. Nine articles with 3324 subjects were included in the meta-analysis. A significantly negative correlation was observed between the GSTM1 null genotype and susceptibility to arsenic poisoning (OR = 0.731; 95% CI: 0.536-0.999; P = 0.049; I2 = 70.5%). There was no significant correlation between the GSTT1 null genotype (OR = 1.009; 95% CI: 0.856-1.189; P = 0.915, I2 = 36.8%) and GSTM1-GSTT1 double null genotype (OR = 1.105; 95% CI: 0.670-1.822; P = 0.695; I2 = 64.7%) and the risk of arsenic poisoning. Egger's and Begg's tests indicated no publishing bias. Compared with controls, individuals with the GSTM1 null genotype were less susceptible to arsenic poisoning. The GSTT1 single null genotype and GSTM1-GSTT1 dual-null genotype were not associated with the risk of arsenic poisoning. The GSTM1 single null genotype may have potential as a genotoxic biomarker to identify individuals who are not prone to arsenic poisoning, and as a reference for guiding the prevention of arsenic poisoning.

Human blood PIG-A mutation and micronucleated reticulocyte flow cytometric assays: Method optimization and evaluation of intra- and inter-subject variation.

We previously described flow cytometry-based methods for scoring the incidence of micronucleated reticulocytes (MN-RET) and PIG-A mutant phenotype reticulocytes (MUT RET) in rodent and human blood samples. The current report describes important methodological improvements for human blood analyses, including immunomagnetic enrichment of CD71-positive reticulocytes prior to MN-RET scoring, and procedures for storing frozen blood for later PIG-A analysis. Technical replicate variability in MN-RET and MUT RET frequencies based on blood specimens from 14 subjects, intra-subject variability based on serial blood draws from 6 subjects, and inter-subject variation based on up to 344 subjects age 0 to 73 years were quantified. Inter-subject variation explained most of the variability observed for both endpoints (≥77%), with much lower intra-subject and technical replicate variability. The relatively large degree of inter-subject variation is apparent from mean and standard deviation values for MN-RET (0.15 ± 0.10%) and MUT RET (4.7 ± 5.0 per million, after omission of two extreme outliers). The influences of age and sex on inter-subject variation were investigated, and neither factor affected MN-RET whereas both influenced MUT RET frequency. The lowest MUT RET values were observed for subjects <11 years old, and males had moderately higher frequencies than females. These results indicate that MN-RET and MUT RET are automation-compatible biomarkers of genotoxicity that bridge species of toxicological interest to include human populations. These data will be useful for appropriately designing future human studies that include these biomarkers of genotoxicity, and highlight the need for additional work aimed at identifying the sources of inter-individual variability reported herein.

Exploration of Cadmium Dioxide Nanoparticles on Bioaccumulation, Oxidative Stress, and Carcinogenic Potential in Oreochromis mossambicus L.

The field of nanotechnology is rapidly expanding with the advancement of novel nanopesticide and nanofertilizers that have the potential for revolutionizing applications in the agricultural industry. Here, we have done chronic toxicity of cadmium dioxide nanoparticles (CdONPs) on fish Oreochromis mossambicus (O. mossambicus) using oxidative stress and genotoxic biomarkers. In this current study, the value of LC50-96 hr of CdONPs has observed 40 μg/ml for O. mossambicus. The three sublethal concentrations, e.g., 4, 10, and 20 μg/ml were selected based on the LC50 value. The fishes were treated to the above concentration of CdONPs for 21 days and were harvested at 1, 7, 14, and 21 days for evaluation of clastogenicity, mutagenicity, and genotoxicity of NPs. Generally, significant effects (p < 0.01) were observed as a dose and duration of exposure. It was observed that lipid peroxidation (LPO) was increased and glutathione was decreased in both tissues. Micronuclei (MNi) were produced significantly in peripheral blood on 21 days at maximum concentration. A similar trend was seen in the damage of DNA with the same manner in terms of the percentage of tail DNA in the lymphocyte, gills, and kidney cells. This study explored the application oxidative stress, comet assay, and micronucleus assay for in situ aquatic laboratory studies using fish O. mossambicus for screening the ecomutagenic and genotoxic potential of environmental pollutants.

ANÁLISIS DE GENOTOXICIDAD EN ERITROCITOS DE TORTUGAS (Phrynops hilarii) DE SITIOS ANTROPIZADOS Y NATURALES DE ENTRE RÍOS, ARGENTINA

The micronucleus test (MN) is a biomarker of non-destructive genotoxicity that allows chromosomal damage and other nuclear alterations (NA) to be detected. Phrynops hilarii is a freshwater chelonium that inhabits regions of central-northern Argentina. The main objective was to determine the presence of MN and other NA in erythrocytes of natural populations of P. hilarii comparing their frequencies between three sites, two anthropized and one of control (cities of Diamante and Paraná) of Entre Ríos, Argentina, during the period 2015-2016. Eighteen individuals (six per sampling site) were evaluated at the sites: 1- PD: Pre-Delta National Park (control), 2- AG: Salto Ander Egg (agroecosystem) and 3- SU: Caleta Club Náutico (urban system). Blood was obtained from the femoral vein. The samples were stained with the May Grünwald-Giemsa method and observed under a microscope with an immersion objective. Micronucleus (MNF) and nuclear alterations (NAF) frequencies were determined every 1000 erythrocytes observed. A significant difference (p&lt;0.05) was found between the PD site and the other sites (AG and SU), both for MNF (p=0.0021) and for NAF (p=0.0011). The highest frequency values ​​corresponded to the AG site (MNF: 3.33 ± 0.62; NAF: 4.67 ± 0.56). Finally, biomonitoring with P. hilarii was useful, so it could be considered as a bioindicator species to assess the quality of Argentina’s environments. Key words: Genotoxicity biomarkers, micronucleus test, nuclear alterations

Analysis of genotoxic effects on plants exposed to high traffic volume in urban crossing intersections

A biological assessment of environmental quality was performed using the tropical plant species Tradescantia pallida (Rose) D.R. Hunt. var. purpurea exposed to different levels of air contamination in urban intersections with high volume of vehicle traffic. Air quality (average daily levels of particulate material in the PM1, 2.5, 10 fractions) and traffic volume in crossing intersections were monitored for 30 days before the collection of plants. Frequency of micronuclei and pollen abortivity in inflorescences collected at different intersections with gradual levels of traffic volume were evaluated as biomarkers of genotoxicity. In addition, the concentrations of bioaccumulated heavy metals in the leaves of the collected plants were also investigated. The proposed biological assessment model found a positive association between the environmental variables (traffic volume; concentration of particulate material) and biological effects (leaf concentration of Cr and Cd; micronucleus frequencies and pollen abortivity).

Antitumor effects of citrinin in an animal model of Sarcoma 180 via cytogenetic mechanisms

Citrinin (CIT) is a cytotoxic, hepatotoxic, nephrotoxic and cardiotoxic metabolite obtained from Penicillium citrinum, that has been increasingly searched as an anticancer drug candidate. In this study, we assessed the antitumor effects of citrinin, using cytogenetic biomarkers for genotoxicity in Sarcoma 180 (S-180) ascitic fluid cells of mice. Citrinin, extracted from P. citrinum acetonitrile extract, was characterized by LC-MS. Cytotoxic assessment was done through using comet (alkaline version) and micronucleus assays. In S-180 cells, CI50 of CIT was 3.77 μg/mL, while at 12.5 and 100 μg/mL, CIT was as cytotoxic as doxorubicin (2 μg/mL). At 0.5, 1.0 and 2.0 μg/mL, it induced genotoxicity and mutagenicity in S-180 cells, especially at 2 μg/mL, triggering oxidative damage similar to hydrogen peroxide (10 mM). The antitumor effects were evidenced by a marked increase in S-180 cells apoptosis and necrosis due to clastogenic and/or aneugenic cytogenetic effects (micronucleus formation), as well as by induction of nucleoplasm bridges and nuclear buds, culminating in S-180 apoptosis and necrosis. CIT has potential as drug candidate for antitumor purposesbyinvolving cytogenetic mechanisms.

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.

The Potential Genotoxic Effects of Antineoplastic Drugs in Occupationally Exposed Nurses

Background: Antineoplastic drugs are commonly used globally. They directly interact with the tumor cell deoxyribonucleic acid and inhibit their growth. These actions are non-selectiveaffecting both tumor cells and healthy cells producing toxic effects. The present study was designed to evaluate oxidative stress and genotoxic effects of antineoplastic drugs in occupationally exposed nurses under routine working conditions. Methods: The studied groups included 28 nurses working in Hematology and Oncology unit, Benha University Hospitals and 20 non exposed subjects that work in academic jobs in Benha Faculty of Medicine, matched in age, gender & socioeconomic status. Malondoaldehyde (MDA) & reduced glutathione (GSH) were measured for all participants as markers of oxidative stress. Extent of DNA damage in leucocytes was also evaluated by comet assay as a biomarker of genotoxicity. Results: There were a significant increase in MDA & reduction in GSH in occupationally exposed subjects than control. Also, extent of DNA damage in the lymphocytes of occupationally exposed participants has a high significance than the controls. The work duration and age had a significant impact on degree of DNA damage. Conclusion: occupationally exposed nurses to antineoplastic agents are at greater risk of oxidative stress with consequent DNA damage and potential genotoxic damage.

Radioprotective Effect of Pioglitazone Against Genotoxicity Induced by Ionizing Radiation in Healthy Human Lymphocytes.

Pioglitazone (PG) is used to control high blood sugar in patients with type 2 diabetes mellitus. PG acts as a peroxisome proliferator-activated receptor γ agonist. In addition to the insulin-sensitizing effect, PG possesses anti-inflammatory effect. In this study, the protective effect of PG was evaluated against DNA damage induced by ionizing radiation in healthy human lymphocytes. The microtubes containing human whole blood were treated with PG at various concentrations (1-50 μM) for three hours. Then, the blood samples were irradiated with X-ray. Lymphocytes were cultured for determining the frequency of micronuclei as a genotoxicity biomarker in binucleated lymphocytes. The mean percentage of micronuclei was significantly increased in human lymphocytes when exposed to IR, while it was decreased in lymphocytes pre-treated with PG. The maximum reduction in the frequency of micronuclei in irradiated lymphocytes was observed at 5 μM of PG treatment (48% decrease). The anti-inflammatory property suggested the mechanism action of PG for protecting human lymphocytes against genotoxicity induced by ionizing radiation.