Genotoxicity Biomarkers Research Articles

DNA damage and oxidative stress induced by imidacloprid exposure in different tissues of the Neotropical fish Prochilodus lineatus

Imidacloprid (IMI), a systemic neonicotinoid insecticide widely used in worldwide scale, is reported in freshwater bodies. Nevertheless, there is a lack of information about IMI sublethal effects on freshwater fish. Thus, the aim of this study was to identify the potential hazard of this insecticide to the South American fish Prochilodus lineatus exposed for 120 h to four IMI concentrations (1.25, 12.5, 125, and 1250 μg L−1). A set of biochemical, genotoxic and physiological biomarkers were evaluated in different organs of the fish. IMI exposure induced significant changes in the enzymatic profiles of P. lineatus, with alterations in the activity of biotransformation and antioxidant enzymes in different tissues. Redox balance of the tissues was affected, since oxidative damage such as lipoperoxidation (LPO) and protein carbonylation (PCC) were evidenced in the liver, gills, kidney and brain of fish exposed to different IMI concentrations. Fish exposed to all IMI concentrations showed decreased blood glucose indicating an increase of energetic demand. DNA damage was evidenced by the comet test, in the erythrocytes of fish all the concentrations evaluated. We integrated these results in the Integrated Biomarker Response (IBR) index, which evidenced that the organs most affected by IMI exposure were the liver and kidney, followed by the gills. Our results highlight the importance of investigating different target tissues after IMI exposure and show the sublethal effects of IMI in some of them; they also warn to the possible consequences that fish living in freshwater ecosystems can suffer due to IMI exposure.

Assessment of the health status and risk of genotoxic and cytotoxic damage in Argentinian adolescents living near horticultural crops.

In some rural areas in Argentina, adolescents may be considered as a group indirectly exposed to agrochemicals because their parents plant small crops near their homes. This could become a health risk to children and adolescents who may be more sensitive to exposure to chemicals than adults. The objective of this study was to evaluate the health status of two different groups of Argentinian adolescents using biochemical parameters, dietary information, and cytogenetic biomarkers of genotoxicity and cytotoxicity. The study groups included 32 adolescents from Montecarlo, who were indirectly exposed to agrochemicals, and 30 unexposed adolescents from Exaltación de la Cruz. The values of total cholesterol, LDL cholesterol, triglycerides, gamma glutamyltransferase, and butyrylcholinesterase (BuChE) were higher (p < 0.05) in males from Exaltación de la Cruz compared with those from Montecarlo. The BuChE activity was also higher (p < 0.05) in females from this region. Furthermore, the consumption of citrus, vegetable-like fruits, tubers, and red meat was more frequent (p < 0.05) in Montecarlo. On the other hand, differences in frequency of biomarkers of genetic damage in lymphocytes were not found (p > 0.05). However, the cytome assay in buccal cells showed that karyorrhectic and pyknotic cells were more frequent (p < 0.05) in the Montecarlo group; whereas, the frequencies of cells with nuclear buds, condensed chromatin and karyolysis were higher (p < 0.05) in the Exaltación de la Cruz group. Despite the differences between the parameters and biomarkers evaluated, the adolescents of Montecarlo did not present health impairment probably due to the type and level of exposure to agrochemicals.

Technology and methodology of DNA adducts analysis

DNA adducts are formed from the covalent reaction of electrophilic molecules to a variety of nucleophilic groups in DNA strands. They could be used as biomarkers for genotoxicity. The formation of DNA adducts caused by toxic chemicals is a critical initiator in the process of gene mutation, developmental malformation and tumor. The development of fast, sensitive and accurate detection technologies and methodologies is the key to understand and study the adverse health effects of DNA adducts. At present, analytical technologies for the detection of DNA adducts mainly include 32P post-labeling, immunoassay, immuno-capillary electrophoresis-laser induced fluorescence, DNA sequencing, and Chromatography-mass spectrometry. In this article, the applications and development prospects of these techniques and methods in DNA adducts analysis are briefly reviewed and discussed.

Are the damaging effects induced by the imazethapyr formulation Pivot® H in Boana pulchella (Anura) reversible upon ceasing exposure?

In the present study, the damage recovery capabilities of Boana pulchella tadpoles after acute exposure (96h) to 0.39mg/L concentration of the imazethapyr (IMZT)-based herbicide formulation Pivot® H (25% IMZT LC50 value) were assessed during a period of 7 to −21 days. To appraise the recovery capabilities, frequency of micronuclei (MNs), other nuclear abnormalities and DNA single-strand breaks evaluated by single cell gel electrophoresis assay on circulating blood cells were employed as endpoints for genotoxicity. Growth, development, body mass, and morphological abnormalities were also employed as individual endpoints in the recovery assay. Results demonstrated that IMZT induced sublethal effects at both the individual (i.e., loss of keratodonts) and cytogenetic levels (e.g., increase of MN frequency, other nuclear abnormalities and DNA single-strand breaks). At 11 days of the exposure phase, tadpoles recovered their basal levels of frequency of MNs, other nuclear abnormalities, and comets. However, loss of keratodonts, observed at the end of the exposure period, was present up to 21 days thereafter. Finally, axial abnormalities and delay in development stage were observed only during the postexposure phase in IMZT-exposed tadpoles at 18 and 25 days, respectively and were observed until the end of the experiment. This is the first evidence of use the comet assay as cytogenetic biomarker of genotoxicity in evaluating the recovery capabilities of amphibians in general and also those of B. pulchella after exposure to IMZT.

The use of genotoxicity biomarkers in molecular epidemiology: applications in environmental, occupational and dietary studies.

Molecular epidemiology is an approach increasingly used in the establishment of associations between exposure to hazardous substances and development of disease, including the possible modulation by genetic susceptibility factors. Environmental chemicals and contaminants from anthropogenic pollution of air, water and soil, but also originating specifically in occupational contexts, are potential sources of risk of development of disease. Also, diet presents an important role in this process, with some well characterized associations existing between nutrition and some types of cancer. Genotoxicity biomarkers allow the detection of early effects that result from the interaction between the individual and the environment; they are therefore important tools in cancer epidemiology and are extensively used in human biomonitoring studies. This work intends to give an overview of the potential for genotoxic effects assessment, specifically with the cytokinesis blocked micronucleus assay and comet assay in environmental and occupational scenarios, including diet. The plasticity of these techniques allows their inclusion in human biomonitoring studies, adding important information with the ultimate aim of disease prevention, in particular cancer, and so it is important that they be included as genotoxicity assays in molecular epidemiology.

Effects of glyphosate on immune responses and haemocyte DNA damage of Chinese mitten crab, Eriocheir sinensis

As a broad-spectrum organophosphorus herbicide, glyphosate is widely utilized around the world. The toxic effects of glyphosate on Chinese mitten crab, Eriocheir sinensis, were assessed using immunotoxicity and genotoxicity biomarkers in this study. The results showed that 24 h and 96 h LC50 values of glyphosate for E. sinensis were estimated as 461.54 and 97.89 mg/L, respectively, and the safe concentration was 4.4 mg/L. According to the results above, glyphosate was applied at concentrations of 0, 4.4, 9.8, 44 and 98 mg/L, for 96 h in the exposure experiment. Total haemocyte count (THC) and percentage of granulocytes decreased significantly following 6 h exposure to each concentration of glyphosate and tended to gradually stabilize after 12 h except in 4.4 mg/L, which rapidly recovered to a normal level in 12 h. Phagocytic activity in all treatments decreased dramatically at 6 h and maintained stability until the 96-h mark. Comet tail has been observed early at 24 h in each treatment, and the comet ratio and percentage of DNA (% DNA) in the tail increased as the exposure experiment progressed. Immune-related enzyme activity varied during the experiment. Acid phosphatase (ACP) and alkaline phosphatase (AKP) activities in 44 and 98 mg/L treatments decreased significantly after 48 h exposure, while AKP activities in all concentrations increased markedly at the beginning of exposure. The superoxide dismutase (SOD) and peroxidase (POD) activities increased significantly after 6 h exposure to 44 and 98 mg/L of glyphosates but decreased at 24 h. In addition, the β-glucuronidase (β-GD) activities in the 9.8, 44 and 98 mg/L groups, increased after 6-h exposure and were significantly higher than those in the control at 96 h. These results indicated that glyphosate has evident toxic effect on E. sinensis by immune inhibition that is possibly due to the haemocyte DNA damage and a sharp decline in haemocyte numbers, which subsequently induced changes in activities of immune-related enzymes and haemocyte phagocytosis.

Lethal and sublethal effects of the pirimicarb-based formulation Aficida® on Boana pulchella (Duméril and Bibron, 1841) tadpoles (Anura, Hylidae)

Acute lethal and sublethal toxicity of the pirimicarb-based commercial formulation Aficida® were evaluated on Boana pulchella tadpoles. Whereas mortality was used as end point for lethality, frequency of micronuclei and other nuclear abnormalities as well as alterations in the frequency of erythroblasts in circulating blood as biomarkers for genotoxicity and cytotoxicity, respectively. Swimming, growth, developmental and morphological abnormalities were also employed as sublethal end points. Results show that the species is within the 13th percentile of the distribution of acute sensitivity of species to pirimicarb for aquatic vertebrates. Results revealed values of 23.78 and 101.45mg/L pirimicarb as LC5096h for GS25 and GS36 tadpoles, respectively. The most evident effects were related with the swimming activity with NOEC and LOEC values within the 0.005–0.39mg/L pirimicarb concentration range. Aficida® induced DNA damage at the chromosomal level by increasing micronuclei frequency and other nuclear abnormalities, i.e., lobbed and notched nuclei and binucleated cells. Cellular cytotoxicity was found after Aficida® treatment. The presence of abdominal oedemas in exposed organisms and thus flotation response of organisms could be proposed as a new sensitive exposure parameter. The multiple end point assessment approach used allowed a complete understanding the multi level of effects occurring by exposure to pirimicarb, at least in B. pulchella.

Effects of ozone exposure on human epithelial adenocarcinoma and normal fibroblasts cells

Previous studies show variable ozone cytotoxicity and genotoxicity in cell cultures, laboratory animals and humans directly exposed to tropospheric ozone. The aim of this study was therefore to investigate and compare the cyto and genotoxic effects of ozone using adenocarcinoma human alveolar basal epithelial cells A549 and normal human fibroblasts Hs27. A cell culture chamber with controlled atmosphere (a simulation reactor) was built to inject a flow of 120 ppb of ozone, which is two times the threshold value for the protection of human health, fixed by the EU legislation. Cell proliferation was evaluated by a luminescent cell viability assay while we assessed the genotoxic potential of ozone by the induction of micronuclei as well as evaluating DNA strand breaks by the induction of micronuclei evaluated by means of the cytokinesis-block micronucleus (CBMN) assay as well as evaluating DNA strand breaks by Alkaline Comet Assay (CA) or Comet Assay. A549 cells viability decreases significantly at 24 hours treatment with 120 ppb of O3 while at 48 hours and 72 hours O3 treated cells viability doesn’t differ in respect to the control. However a significative decrease of A549 viability is shown at 72 hours vs. 48 hours in both treated and not-treated cells. The viability trend in the Hs27 cells did not show any significant changes in treated samples compared to the control in all conditions. The two genotoxicity biomarkers, the micronucleus and the comet tests, showed in both the cell types exposed to ozone, a significant increase in the number of micronuclei and in the tail DNA % in respect to the control even if at different times/cell type. Moreover, we found that O3 provokes genotoxic effects more evident in A549 cancer cells than in normal fibroblasts Hs27 ones. We applied a cell growth simulation model referred to ozone treated or not cell lines to confirm that the ozone exposure causes a slackening in the cells replication.

Is mobile phone radiation genotoxic? An analysis of micronucleus frequency in exfoliated buccal cells

Electromagnetic fields (EMF) are classified as “possibly carcinogenic” by the International Agency for Research on Cancer (IARC). Some publications have reported associations between EMF exposure and DNA damage, but many other studies contradict such findings. Cytomorphological changes, such as micronuclei (MN), indicative of genomic damage, are biomarkers of genotoxicity. To test whether mobile phone-associated EMF exposure affects the MN frequency in exfoliated buccal cells, we obtained cells smears from the left and right inner cheeks of healthy mobile phone users, aged 18–30 (n=86), who also completed a characterization survey. MN frequencies were tested for potential confounding factors and for duration of phone use and preferential side of mobile phone use.No relationship was observed between MN frequency and duration of mobile phone use in daily calls. Cells ipsilateral to mobile phone use did not present a statistically significantly higher MN frequency, compared to cells contralateral to exposure. A highly statistically significant (p<0.0001) increase in MN frequency was found in subjects reporting regular exposure to genotoxic agents. Therefore, our results suggest that mobile phone-associated EMF do not to induce MN formation in buccal cells at the observed exposure levels.

The lymphocyte cytokinesis block micronucleus test in human populations occupationally exposed to vinyl chloride: A systematic review and meta-analysis.

Vinyl chloride (VC) is widely used in industry in the production of polyvinyl chloride (PVC), which is used to manufacture a large variety of materials. VC was classified as a known (Group 1) human carcinogen by IARC on the basis of increased risk for liver angiosarcoma and hepatocellular cancer, and the carcinogenicity of VC was shown to be mediated by a genotoxic mechanism. Following inhalation, the compound is rapidly absorbed and metabolized in the liver to the electrophilic metabolites chloroethylene-oxide and chloroacetaldehyde, which form DNA adducts that can be processed into point mutations in cancer-related genes detected in humans and rats exposed to VC. A number of genotoxicity biomarkers were applied in workers exposed to VC to detect early biological responses associated with the carcinogenesis process. The present systematic review analyzed the published studies in which the cytokinesis-block micronucleus assay in peripheral lymphocytes (L-CBMN) was applied in VC-exposed subjects. Thirteen out of fifteen retrieved studies performed in China showed increased MN frequencies (FR 1.92-3.98) associated with increased cumulative exposure or employment time. Twofold and more than threefold increases were detected in PVC-exposed workers exposed to a mean of 50ppm of VC in the former Yugoslavia and in South India, respectively. The meta-analysis of MN frequency from six eligible studies confirmed this tendency (pooled MR 2.32 - 95% CI 1.64-3.27). The benchmark dose lower limit for 10% excess risk (BMDL 10) calculated from three studies resulted in an estimated exposure limit of 0.03-0.07mg/m3. Overall the results of this review showed the need for further studies, especially because PVC products from China may contain high levels of uncoupled VCM that could represent a source of exposure to workers and consumers. Moreover, the results underline the importance of re-evaluating the recommended exposure limits using new biomonitoring methods in addition to MN.

Assessment of genotoxicity amongst smokers, alcoholics, and tobacco chewers of North India using micronucleus assay and urinary 8-hydroxyl-2'-deoxyguanosine, as biomarkers.

The main objective of the present study was to screen the genotoxicity caused by individual and combined habits of smoking, tobacco chewing, and alcohol consumption in human population of North India. Study recruited 67 male subjects aged 25 to 65years. Buccal mucosal cells were subjected to micronucleus (MN) assay, and 8-hydroxyl-2-deoxyguanosine (8-OHdG) was estimated in their urine samples. Number and shape of the MN cells varied in the buccal epithelium of different groups. Maximum number of MN (0.47%) were found in tobacco chewers followed by smokers (0.45%) and alcoholics (0.44%) (P<0.05). These results reciprocated the concentration of urinary 8-OHdG. Maximum value for 8-OHdG was also recorded in tobacco chewers (21.07±5.51mg/mg creatinine) followed by smokers (20.25±3.96mg/mg creatinine) and alcoholics (19.06±3.41mg/mg creatinine) (P<0.05). Combined effects of these agents were found to be statistically different from individual effects. Carcinogenic compounds present in cigarette smoke, nitrosamines found in solid tobacco, and acetaldehyde, a metabolic product of alcohol, induce oxidative stress that manifests into genotoxicity. In conclusion, demographical differences occur in the genotoxicity caused by these three habits. MN assay and urinary 8-OHdG are simple, noninvasive, and reliable biomarkers of genotoxicity.

Multi-endpoint biological monitoring in combined, carcinogenic occupational exposures

We aimed to develop a relevant multi-endpoint biomonitoring system by studying different genotoxicity biomarkers in complex carcinogenic exposures under occupational situations. Altogether 109 workers were followed in five different workplaces. The combined carcinogenic exposures were monitored in the urine and peripheral blood samples using Ames mutagenicity test and cytogenetic analyzes. The different genotoxicity endpoints studied showed different results in the same carcinogenic exposure situations. The urinary mutagenicity tests provided more information and proved to be more sensitive compared to the cytogenetic tests in the majority of cases. In complex exposures multistep biomonitoring panel should be applied, because the exact mechanisms of the combination of single exposing agents are not known. Such a panel should involve monitoring different endpoints, e.g. point mutations, chromosomal mutations. A relatively affordable and rapid testing panel was developed using validated tests as Ames and cytogenetic assays, but its practical use should be confirmed by further investigations.

Ecological risk assessment in a tropical wetland contaminated with gasoline: Tier 1

ABSTRACTTo assess natural attenuation and the efficiency of remediation actions after more than two years a large accident with gasoline spill contaminated a wetland in a tropical region, an Ecological Risk Assessment based on the Dutch Triad was applied. In total, eight surface water-sampling points were distributed randomly in the affected area and on reference area upstream the contaminated site, with similar ecological characteristics. Risks based on chemical, ecotoxicological, and ecological lines of evidence (LoE) were calculated to integrate the environmental risk indexes. The chemical risk was derived from toxic pressure coefficients based on the total BTEX and naphthalene concentrations. Ecotoxicological LoE based on acute toxicity with Daphnia similis and Aliivibrio fischeri bioassays and chronic toxicity with Desmodesmus subspicatus bioassay contributed to raise uncertainty due to low sensitivity of acute assays. Genotoxicity and endocrine disruption biomarkers of Oreochromis niloticus were used to calculate the Biomarker Stress Index (BSI) assumed as Ecological Risk Index. The integration of the Chemical Risk Index with BSI to estimate the Biological Vulnerability Index allowed a meaningful analysis of the threats to the aquatic ecosystem, thereby supporting managers and decision-makers.

Assessment of toxicological effects of raw and bioremediated olive mill waste in the earthworm Eisenia fetida: A biomarker approach for sustainable agriculture

The olive oil extraction process produces large amounts of olive mill waste (OMW) that can be re-used in agriculture by land spreading. OMW has a low pH, high salinity and high levels of polyphenols and is potentially dangerous for the environment. It is therefore mandatory to develop procedures able to produce OMW with lower environmental impact. The first aim of the present study was to evaluate the toxicological effects of two different typologies of OMW: raw Two-Phase Olive Mill Waste (TPOMW) and raw Olive Mill Waste Waters (OMWW), on a soil bioindicator, the earthworm Eisenia fetida, using neurotoxicity (AChE), oxidative stress (LPO, CAT) and genotoxicity (comet assay) biomarkers. The second aim was to test the efficacy of a composting/bioaugmentation process by investigating the toxicological effects of the bioremediated OMW. E. fetida was exposed for 72h to increasing concentrations (12.5, 25, 50%) of raw and bioremediated TPOMW and OMWW in an artificial soil (50% potting soil+50% quartz sand). Raw OMW caused earthworm mortality at high doses and measurable biochemical and cellular effects at lower doses. The main cause of these effects is probably the high level of polyphenols present in the OMW. Neurotoxic effects, induction of oxidative stress and genotoxic effects were highlighted. The most evident toxicological effects were produced by the TPMW. The evaluation of the bioremediation process efficacy revealed that a high decrease in acidity and polyphenol content corresponds to a decrease of toxicological effects. This study contributed to assess the environmental sustainability of the bioremediated OMWs, to be used as fertilizers in agriculture.

Ameliorative Effect of Eugenol and Anethole on Arsenic Induced Oxidative DNA Damage in Cultured Human Peripheral Blood Lymphocytes

Arsenic contamination is one of the major health concerns all over the world and associated with various types of cancer and pathological effects. The production of reactive oxygen species (ROS) plays a crucial role in arsenic mediated toxicity. Several studies have shown that population constantly exposed to arsenic have substantial oxidative stress that, in turn, induces DNA damage. In the present work eugenol and anethole were investigated for their protective effect against arsenic mediated oxidative DNA damage in peripheral blood lymphocytes. Comet assay and lipid peroxidation was used as biomarker of genotoxicity and oxidative stress respectively. A dose dependent increase in tail moment and lipid peroxidation was observed when lymphocytes were treated with sodium arsenite. Treatment of arsenic (50?M) along with eugenol (20?M) and anethole (50?M) showed a significant decrease in the tail moment and lipid peroxidation in cultured peripheral blood lymphocytes. The decrease in the tail moment and lipid peroxidation was significantly higher in combined supplementation of eugenol and anethole as compared to individual administration. The results of the present study suggests ameliorative role of eugenol and anethole against arsenic induced genotoxic and oxidative damage in cultured human peripheral blood lymphocytes.

Environmental risk assessment in five rivers of Parana River basin, Southern Brazil, through biomarkers in Astyanax spp.

In the current study, water quality of five river sites in Parana River basin (Brazil), utilized for public water supply, was assessed through a set of biomarkers in fish Astyanax spp. Population growth and inadequate use of land are challenges to the preservation of biodiversity and resources such as water. Some physicochemical parameters as well as somatic indexes, gills and liver histopathology, genotoxicity, and biochemical biomarkers were evaluated. The highest gonadosomatic index (GSI) and antioxidant parameters (catalase and glutathione S-transferase activities, non-protein thiols), as well as the lowest damage to biomolecules (lipid peroxidation, protein carbonylation, DNA damage) were observed in site 0 (Piava River), which is located at an environmental protected area. Site 1, located in the same river, but downstream site 0 and outside the protection area, presents some level of impact. Fish from site 2 (Antas River), which lack of riparian forest and suffer from silting, presented the highest micronucleus incidence and no melanomacrophages. Differently, individuals from site 3 (Xambrê River) and site 4 (Pinhalzinho River) which receive surface runoff from Umuarama city, urban and industrial sewage, have the highest incidences of liver and gill histopathological alterations, including neoplasia, which indicated the worst health conditions of all sites. In particular, site 4 had high levels of total nitrogen and ammonia, high turbidity, and very low oxygen levels, which indicate important chemical impact. Comparison of the biomarkers in fish allowed classification of the five sites in terms of environmental impact and revealed that sites 3 and 4 had particular poor water quality.

Pollutants Induced Oxidative Stress, DNA Damage and Cellular Deformities in Clarias gariepinus (Burchell), from River Yamuna in Delhi Region, India.

The purpose of the present study was to evaluate the severity of pollution impact at two extreme sites of river Yamuna in Delhi region utilizing oxidative stress, genotoxic and histopathological biomarkers in gonad (ovary) of Clarias gariepinus. To evaluate oxidative stress, TBAR's and ferric reducing antioxidant power (FRAP) assay were employed while comet assay and classic histology were used to estimate genotoxicity and cellular damage respectively. The results indicated significant increase (p < 0.001) in TBARs level (µmol/g wet tissue); significant decrease (p < 0.001) in FRAP value (U/mg tissue), significant increase (p < 0.001) in DNA damage and extensive abnormal histoarchitecture in ovarian samples procured from Okhla as compared to Wazirabad barrage. Thus, exposure to the increasing toxicity downstream the river is altering the activity of cellular total antioxidant capacity persuading oxidative stress and cellular damage, eventually distressing the heath of fish fauna directly and humans indirectly.

Evaluation of imazethapyr-induced DNA oxidative damage by alkaline Endo III- and Fpg-modified single-cell gel electrophoresis assay in Hypsiboas pulchellus tadpoles (Anura, Hylidae)

Imazethapyr (IMZT) is a selective postemergent herbicide with residual action. Available data analyzing its effects in aquatic vertebrates are scarce. In previous studies, we demonstrated that IMZT induces lesions into the DNA of Hypsiboas pulchellus tadpoles using the single-cell gel electrophoresis (SCGE) assay as a biomarker for genotoxicity. Currently, this assay can be modified by including incubation with lesion-specific endonucleases, e.g., endonuclease III (Endo III) and formamidopyrimidine-DNA glycosylase (Fpg), which detect oxidized pyrimidine and purine bases, respectively. The aim of this study was to evaluate the role of oxidative stress in the genotoxic damage in circulating blood cells of H. pulchellus tadpoles exposed to the IMZT-based Pivot H® formulation (10.59% IMZT) at a concentration equivalent to 25% of the LC50 (96h) value (0.39mg/L IMZT) during 48 and 96h. Our results demonstrate that the herbicide induces oxidative DNA damage on H. pulchellus tadpoles at purines bases but not at pyrimidines. Our findings represent the first evidence of oxidative damage caused by IMZT on anuran DNA using the alkaline restriction enzyme-modified SCGE assay.

Genotoxic and Biochemical Biomarker Responses in Meretrix Casta Exposed to Environmentally Relevant Concentrations of Cadmium

Genotoxic and Biochemical Biomarker Responses in Meretrix Casta Exposed to Environmentally Relevant Concentrations of Cadmium

Genotoxicity study of nickel oxide nanoparticles in female Wistar rats after acute oral exposure.

Nanoparticles (NPs) apart from their widespread advantages and increased utilisation, have aroused concerns over their safe use. Nickel (II) oxides (NiO) NPs are used as catalysts, biosensors and in many of the consumer products. The increasing use of NiO NPs necessitates an improved understanding of their potential impact on the environment and human health. In this study, we investigated the acute genotoxic effects of NiO NPs by oral route administration with three different doses (125, 250 and 500 mg/kg bw). Before the in vivo toxicological evaluation, characterisation of particles by Transmission Electron Microscopy, X-ray diffraction, Dynamic Light Scattering (DLS) and Laser Doppler Velocimetry analysis was performed. Genotoxicity biomarkers such as comet, micronucleus and chromosomal aberrations (CAs) assays were utilised in this study. To document the uptake, retention and elimination of the NPs, biodistribution studies were also performed. The particle size obtained from Transmission Electron Microscopy analysis for NiO NPs was 15.62 ± 2.59 nm. The mean hydrodynamic diameter and PdI of NiO NPs in Milli-Q water suspension obtained by DLS was 168.9 ± 17.13 nm and 0.375, respectively. Comet assay revealed significant (P < 0.001) DNA damage at 500 mg/kg bw dose in the PBL, liver and kidney cells of rats at the 24-h sampling time. The result of micronucleus and CAs tests was in agreement with the comet assay data. Biodistribution of NiO NPs revealed a maximum accumulation of Ni in the liver tissue at the 24-h sampling time. Our study showed significant DNA damage at the high dose level and the effect was more prominent at 24-h sampling time, providing preliminary evidence that the NiO NPs are capable of inducing genotoxicity when administered through the oral route. However, mechanistic investigations are needed before drawing any firm conclusion regarding the toxicology of NiO NPs.