Terms Of Genotoxicity Research Articles

Single versus intermittent cycle exposure effect of 6-mercaptopurine in juvenile Sprague-Dawley rat: a germ cell-specific mechanistic study.

Infertility is a frequent long-term adverse effect of cancer therapy for children. Compromised testicular functions in adolescence are frequent observations after chemotherapy and there are currently no well-established alternatives to avoid this damage. Antimetabolites such as 6-mercaptopurine (6-MP) are used to treat a variety of cancer; however, its treatment-associated adverse effects on the male reproductive functions are overlooked. Here, the molecular processes underlying 6-MP-induced male germ cell damage in juvenile Sprague-Dawley (SD) rats (3weeks) have been investigated. Rats were administered with low (5mg/kg), medium (10mg/kg), and high (20mg/kg) doses of 6-MP per orally either singly (1week × 1 cycle) or intermittently (1week treatment followed by 1week remission period × 3 cycles). The toxicity was evaluated in terms of genotoxicity and testes- and sperm-related cellular and molecular parameters. Single cycle of exposure either produced mild or no toxic manifestations at the end of the 6th week. Intermittent cycles of exposure, particularly at the 10 and 20mg/kg, decreased body and organ weights, increased micronucleated cells in the peripheral blood, induced oxidative/nitrosative stress, altered sperm chromatin quality, reduced serum testosterone and follicle stimulating hormone (FSH) levels, increased testicular structural aberrations, DNA damage, and apoptosis, and upregulated TNF-α expression and downregulated p-AMPK and β-catenin expressions. Conclusively, intermittent cycles of exposure at 10 and 20mg/kg doses to the juvenile rats significantly induced oxidative stress, genotoxicity, and cellular and molecular perturbations in the testes and sperm of adult rats.

Biocompatibility of Membranes Based on a Mixture of Chitosan and Lythri herba Aqueous Extract

In the current context of concern for the improvement and protection of environmental conditions, emphasis is placed on the provision of non-toxic, eco-friendly, renewable biomaterials to replace established chemical substances. Lythri herba is the aerial part of the plant species Lythrum salicaria L., known in the scientific literature especially for its content of tannins and total polyphenols, which highlight its antioxidant, hemostatic, antibacterial and antidiarrheal properties. Chitosan is a biopolymer widely used in industry and medicine due to its abundance in nature, its biodegradability, lack of toxicity and the ease with which it can be transformed into several basic forms (hydrogel, membrane, sponge). The aqueous solutions and membranes obtained in this study by merging these two natural resources were biologically tested in terms of genotoxicity (SOS-Chromo assay), hemolytic activity, thrombin generation activity and bacterial adhesion to reveal outwardly the lack of these properties and their use for medical purposes. The results of the current study attest to the absence of mutagenic and slight hemolyzing properties, thus supporting the possibility of using this extract and membrane in medical and pharmaceutical therapeutic practice. The surface parameters of membranes were examined and important influences at thrombin activity were found. Also, bacterial adhesion results showed a correlation between Lythri herba and chitosan concentrations and membranes’ appearances (swelling, stability). The results show that the membranes could be a promising material for biomedical applications.

Genotoxicity and endocrine disruption potential of haloacetic acids in human placental and lung cells

Chlorination of water results in the formation of haloacetic acids (HAAs) as major disinfection byproducts (DBPs). Previous studies have reported some HAAs species to act as cytotoxic, genotoxic, and carcinogenic. This work aimed at further exploring the toxicity potential of the most investigated HAAs (chloroacetic (CAA), bromoacetic (BAA), iodoacetic (IAA) acid) and HAAs species with high content of bromine (tribromoacetic acid (TBAA)), and iodine in their structures (chloroiodoacetic (CIAA) and diiodoacetic acid (DIAA)) to human cells. Novel knowledge was generated regarding cytotoxicity, oxidative stress, endocrine disrupting potential, and genotoxicity of these HAAs by using human placental and lung cells as in vitro models, not previously used for DBP assessment. IAA showed the highest cytotoxicity (EC50: 7.5 μM) and ability to generate ROS (up to 3-fold) in placental cells, followed by BAA (EC50: 20–25 μM and 2.1-fold). TBAA, CAA, DIAA, and CIAA showed no significant cytotoxicity (EC50 > 250 μM). All tested HAAs decreased the expression of the steroidogenic gene hsd17b1 up to 40 % in placental cells, and IAA and BAA (0.01–1 μM) slightly inhibited the aromatase activity. HAAs also induced the formation of micronuclei in A549 lung cells after 48 h of exposure. IAA and BAA showed a non-significant increase in micronuclei formation at low concentrations (1 μM), while BAA, CAA, CIAA and TBAA were genotoxic at exposure concentrations above 10 μM (100 μM in the case of DIAA). These results point to genotoxic and endocrine disruption effects associated with HAA exposure at low concentrations (0.01–1 μM), and the usefulness of the selected bioassays to provide fast and sensitive responses to HAA exposure, particularly in terms of genotoxicity and endocrine disruption effects. Further studies are needed to define thresholds that better protect public health.

Effects of Aqueous Dispersions of C60, C70, and Gd@C82 Fullerenes on DNA Oxidative Damage/Repair and Apoptosis in Human Embryonic Lung Fibroblasts.

Fullerenes and metallofullerenes play an active role in homeostasis of reactive oxygen species and may cause oxidative damage to cells. As pristine fullerenes are a basis for derivatization, studying oxidative DNA damage/repair and apoptosis is important in terms of genotoxicity and cytotoxicity for their biomedical application. Aqueous dispersions of C60, C70, and Gd@C82 (5 nM and 1.5 μM) were cultured with human fetal lung fibroblasts for 1, 3, 24, and 72 h. Oxidative DNA damage/repair was assessed through concentration of 8-oxodG, double-strand breaks, and activation of BRCA1. Activity of apoptosis was assessed through the BCL2/BAX ratio. All three fullerenes caused oxidative modification of DNA at the early stages; C60 caused the most long-term damage, Gd@C82 caused the most short-term damage, and C70 caused "wave-like" dynamics. The dynamics of DNA repair correlated with the dynamics of oxidative damage, but Gd@C82 caused more prolonged activation of the repair system than C60 or C70. The oxidative toxicity of Gd@C82, is minor and the oxidative toxicity of C60 is mild and short-term, in contrast to C70. In relation to the studied effects, the fullerenes can be arranged in a safety row of Gd@C82 > C60 > C70.

Methomyl has clastogenic and aneugenic effects and alters the mitotic kinetics in Pisum sativum L.

Methomyl is a carbamate pesticide that is frequently applied to crops all over the world. This research aims to evaluate the Pisum sativum L mitotic process and potential genotoxicity. The Cell Proliferation Kinetics (CPK) frequencies demonstrated changes in kinetics of mitotic process, and study of Mitotic Index (MI) demonstrated that methomyl had cytotoxic properties. In fact, the telophases ratio dropped at 0.1% to 0.5% methomyl treatment, while there was an increase in prophases, metaphases, and anaphases from 0.1% to 0.5% in a dose dependent manner. In terms of genotoxicity, methomyl cause an increase in the frequency of clastogenic and aneugenic chromosomal abnormalities at metaphase-anaphase at 0.1% to 0.5%. The effects on the mitotic spindle were further confirmed by an increase in the frequencies of c-mitosis from 0.1 to 0.5% methomyl treatment. The outcome of the current analysis indicates that regularly used insecticides methomyl has a considerable cytotoxic effect on mitotic cells of Pisum sativum L.

Genotoxicity Comparison between Morinda citrifolia Fruit and Seed Substances.

This study aimed to evaluate the genotoxic potential of the fruit and seed powder, fruit puree, and aqueous extracts of Morinda citrifolia (Rubiaceae, noni). The genotoxic potential of the noni substances was evaluated using in vitro Ames, in vitro chromosomal aberration, and in vivo micronucleus tests. All test procedures were conducted per Organization for Economic Cooperation and Development guidelines, and good laboratory practice. None of the noni fruit test substances showed genotoxic signs up to 5000 and 2000 μg/plate in the Ames and micronucleus tests, respectively. In the chromosomal aberration test, neither the fruit puree nor aqueous extract showed structural and numerical aberrations up to 5000 and 4650 μg/mL, respectively, irrespective of metabolic activation, in both 6 h and 24 h treatment groups. The safe ranges of noni fruit and seed powders were up to 2500 and 2100 μg/mL, respectively, in the 6 h treatment group and up to 1600–4100 and 370–450 μg/mL, respectively, in both 6 h and 24 h treatment groups in the presence of metabolic activation. Noni fruit and seeds were safe in terms of genotoxicity under our experimental conditions. Our data are the first to provide valuable genotoxic information on Morinda citrifolia.

Evaluation of Subchronic Toxicity and Genotoxicity of Ethanolic Extract of Aster glehni Leaves and Stems

Aster glehni, a traditional plant on Ulleung Island in the Republic of Korea, has been recognized for its multiple medicinal properties. However, potential toxicity and safety analyses of A. glehni have not been previously investigated. Therefore, this study aimed to evaluate the safety profile of ethanolic extract of A. glehni leaves and stems (EAG) in terms of genotoxicity and subchronic oral animal toxicity under OECD guidelines and GLP conditions. Toxicological assessments were performed at doses of 1,250, 2,500, and 5,000 mg/kg/day in a 13-week oral repeated-dose toxicity study of EAG in male and female SD rats. In addition, an Ames test, an in vitro mammalian chromosomal aberration test, and a micronucleus test were performed. No toxicological changes in clinical signs, body weights, water and food consumption, urinalysis, hematology, clinical biochemistry, gross findings, and histopathological examinations were observed in subchronic oral animal toxicity. In addition, EAG gave negative results when evaluated using in vitro and in vivo genotoxicity tests. In conclusion, the no-observed-adverse-effect level (NOAEL) of EAG was considered to be 5,000 mg/kg/day, and no target organs were identified in both sexes of rats. EAG was also classified as nonmutagenic and nonclastogenic in genotoxicity testing. Collectively, these results show a lack of general toxicity and genotoxicity for EAG that supports clinical work for development as a herbal medicine.

Comparison of the in vivo genotoxicity of electronic and conventional cigarettes aerosols after subacute, subchronic and chronic exposures.

Tobacco smoking is classified as a human carcinogen. A wide variety of new products, in particular electronic cigarettes (e-cigs), have recently appeared on the market as an alternative to smoking. Although the in vitro toxicity of e-cigs is relatively well known, there is currently a lack of data on their long-term health effects. In this context, the aim of our study was to compare, on a mouse model and using a nose-only exposure system, the in vivo genotoxic and mutagenic potential of e-cig aerosols tested at two power settings (18 W and 30 W) and conventional cigarette (3R4F) smoke. The standard comet assay, micronucleus test and Pig-a gene mutation assay were performed after subacute (4 days), subchronic (3 months) and chronic (6 months) exposure. The generation of oxidative stress was also assessed by measuring the 8-hydroxy-2'-deoxyguanosine and by using the hOGG1-modified comet assay. Our results show that only the high-power e-cig and the 3R4F cigarette induced oxidative DNA damage in the lung and the liver of exposed mice. In return, no significant increase in chromosomal aberrations or gene mutations were noted whatever the type of product. This study demonstrates that e-cigs, at high-power setting, should be considered, contrary to popular belief, as hazardous products in terms of genotoxicity in mouse model.

Design, synthesis and activity against Staphylococcus epidermidis of 5-chloro-2- or 5-chloro-4-methyl-9H-xanthen-9-one and some of its derivatives.

Ten new xanthone derivatives have been designed and synthesized for their potential antibacterial activity. All compounds have been screened against Staphylococcus epidermidis strains ATCC 12228 and clinical K/12/8915. The highest antibacterial activity was observed for compound 3: 5-chloro-2-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)-9H-xanthen-9-one dihydrochloride, exhibiting MIC of 0.8µg/ml against ATCC 12228 strain, compared to linezolid (0.8µg/ml), ciprofloxacin (0.2µg/ml) or trimethoprim and sulfamethoxazole (0.8µg/ml). For the most active compound 3, genotoxicity assay with use of Salmonella enterica serovar Typhimurium revealed safety in terms of genotoxicity at concentration 75µg/ml and antibacterial activity against Salmonella at all higher concentrations. A final in silico prediction of skin metabolism of compound 3 seems promising, indicating stability of the xanthone moiety in the metabolism process.

The Beast of Beauty: Environmental and Health Concerns of Toxic Components in Cosmetics

Cosmetic products are used in large quantities across the world. An increasing number of chemical compounds are being added to the formulation of cosmetic products as additives, fragrances, preservatives, stabilizers, surfactants, dye and shine to potentiate their quality, property and shelf life. Owing to their widespread use, active residues of cosmetic products are continuously introduced into the environment in several ways. Many of these chemicals are bioactive and are characterized by potential bioaccumulation ability and environmental persistence, thus exerting a major risk to humans and the health of ecosystems. Hence, the indiscriminate consumption of cosmetics may present a looming issue with significant adverse impacts on public health. This review intends to spotlight a current overview of toxic ingredients used in formulating cosmetics such as parabens, triclosan, benzalkonium chloride, 1,4-dioxane, plastic microbeads, formaldehyde, diazolidinyl urea, imidazolidinyl urea, sunscreen elements (organic and inorganic UV filters) and trace metals. Specific focus is given to illustrate the biological risks of these substances on human health and aquatic system in terms of genotoxicity, cytotoxicity, neurotoxicity mutagenicity, and estrogenicity. In addition to conclusive remarks, future directions are also suggested.

Evaluation of the cytotoxic and genotoxic effects of different universal adhesive systems.

Objectives:The objective of this study was to evaluate and compare the cytotoxicity and genotoxicity of different universal adhesive systems in the mouse fibroblast cell line L929.Materials and Methods:L929 (mouse fibroblast) cells were exposed to G-Premio Bond (GPB) (GC Europe, Belgium), Prime&Bond Universal (Dentsply Sirona, USA), Universal Bond Quick (Kuraray, USA), Single Bond (SB) Universal (3M ESPE, USA), and Tokuyama Universal Bond (TB) (Tokuyama, USA). Cell viability was assessed by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide test, whereas oxidative DNA damage was assessed by determining the 8-hydroxydeoxyguanosine level using an enzyme-linked immunoassay kit. Statistical analysis was performed by one-way analysis of variance, followed by Bonferroni post hoc tests.Results:Cytotoxic and genotoxic effects of TB and SB Universal groups were significantly higher than the other groups (P < 0.05). Among the adhesives tested, GPB (93.0 ± 1.3) had the least cytotoxicity, while TB (67.3 ± 3.0) had the most cytotoxic effect. In terms of genotoxicity, GPB (2.2 ± 0.3) had the least genotoxic effect, while Tokuyama Bond Universal (4.17 ± 0.4) had the most genotoxic effect.Conclusions:Universal adhesive systems used in dentistry have cytotoxic and genotoxic effects in live cells. Universal adhesive systems should, therefore, be used with caution due to their cytotoxic and genotoxic effects in clinical applications.

Comparison of Impact of Residual Radioactivity Versus Pesticide-Derived Soil Pollution on Genotoxicity

A comparative analysis was performed of the impact on living organisms, in terms of genotoxicity, of two factors, namely, radiation (residual 137Cs) and a chemical factor (pesticides) . The experiment was conducted both on individual pesticide samples and the aqueous extracts of soil samples. Soil samples were collected in the territory of the Orel region (Russia) from May 12 to May 15, 2010, i.e., years after the Chernobyl accident. Changes in the mutagenic index derived from Ames assay (Salmonella/microsomes) and the data obtained from mammalian cell culture in the Cricetulus griseus test (Chinese hamster) of the soil samples arising from the cesium radioactivity and the content of pesticides in these samples were considered. No direct correlation was found between dose level and genotoxicity at low radiation doses (20 μR/h), i.e., correlation with DNA mutations produced, both in terms of frameshifting and the base replacement type. On the contrary, a clear tendency was observed for increase in genotoxicity with increase in the concentration of pesticides and the entire amount of anthropogenic toxicants in the studied soil samples.

In vitro impact of amino acid-derived bacterial metabolites on colonocyte mitochondrial activity, oxidative stress response and DNA integrity

Background4-hydroxyphenylacetic acid (HO-PAA) is produced by intestinal microbiota from L-tyrosine. High concentrations in human fecal water have been associated with cytotoxicity, urging us to test HO-PAA's effects on human colonocytes. We compared these effects with those of phenylacetic acid (PAA), phenol and acetaldehyde, also issued from amino acids fermentation. MethodsHT-29 Glc−/+ human colonocytes were exposed for 24 h to metabolites at concentrations between 350 and 1000 μM for HO-PAA and PAA, 250-1500 μM for phenol and 25-500 μM for acetaldehyde. We evaluated metabolites'cytotoxicity with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide and DNA quantification assays, reactive oxygen species (ROS) production with H2DCF-DA, and DNA damage with the comet assay. We measured cell oxygen consumption and mitochondrial complexes activity by polarography. ResultsAlthough HO-PAA displayed no cytotoxic effect on colonocytes, it decreased mitochondrial complex I activity and oxygen consumption. This was paralleled by an increase in ROS production and DNA alteration. Cells pretreatment with N-acetylcysteine, a ROS scavenger, decreased genotoxic effects of HO-PAA, indicating implication of oxidative stress in HO-PAA's genotoxicity. PAA and phenol did not reproduce these effects, but were cytotoxic towards colonocytes. Last, acetaldehyde displayed no effect in terms of cytotoxicity and mitochondrial metabolic activity, but increased DNA damage. ConclusionsSeveral bacterial metabolites produced from amino acids displayed deleterious effects on human colonocytes, in terms of genotoxicity (HO-PAA and acetaldehyde) or cytotoxicity (PAA and phenol). General significanceThis study helps understanding the consequences of intestinal microbiota's metabolic activity on the host since amino acids fermentation can lead to the formation of compounds toxic towards colonic epithelial cells.

Assessment of toxic effects of the antibiotic erythromycin on the marine fish gilthead seabream (Sparus aurata L.) by a multi-biomarker approach

Erythromycin (ERY) is one of the most common antibiotics used in human and veterinary practices, leading to ubiquitous environmental distribution and possible toxicity to non-target organisms. The purpose of this study was to determine sub-lethal effects of ERY towards the marine fish Sparus aurata (gilthead seabream). S. aurata were acutely (0.3–323 μg/L, 96 h) and chronically (0.7–8.8 μg/L, 28 d) exposed to ERY. Detoxification [7-ethoxyresorufin O-deethylase (EROD), glutathione S-transferases (GSTs), uridine-diphosphate-glucuronosyltransferase (UGT)], oxidative stress [catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GRed)], lipid peroxidation [thiobarbituric acid reactive substances - (TBARS)], genotoxicity [genetic damage index (GDI) and erythrocytic nuclear abnormalities (ENAs)], neurotransmission [acetylcholinesterase (AChE)] and energy metabolism [lactate dehydrogenase (LDH)] biomarkers were evaluated. Results showed that ERY did not promote significant effects in detoxification biomarkers, but induced slight pro-oxidative effects (decrease of GPx activity in the liver after acute exposure and an increase in gills after chronic exposure; and an increase of hepatic GRed activity following chronic exposure). There was a significant decrease in TBARS after chronic exposure, which contradicts a full scenario of oxidative stress. In terms of genotoxicity, both ERY exposures caused only a significant increase of GDI. Neurotransmission and energy metabolism were not also affected by ERY. Although few toxic effects of ERY have been previously documented (involving different metabolic pathways, as tested in this work), these were mainly observed for freshwater species. These findings suggest low vulnerability of S. aurata to ERY at levels close to the ones found in the wild.

Toxicology of Pre-heated Composites Polymerized Directly and Through CAD/CAM Overlay.

ObjectivesThe aim was to compare cytotoxicity/genotoxicity of pre-heated composites polymerized through CAD/CAM overlays on isolated human peripheral blood lymphocytes.Material and MethodsA microhybrid (Z100, 3M ESPE) and nanofilled composite (Filtek Supreme Ultra, 3M ESPE) were heated in a heating unit (Calset, AdDent Inc.) at different temperatures: 37 oC, 54 oC, and 68 oC. A small amount of heated composite was placed in a cylindrical mold (6mm diameter; 0.65mm thick), covered with a Mylar sheet, pressed and light-cured directly and through 2 mm thick CAD/CAM ceramic-reinforced polymer (CRP)(LAVA Ultimate, 3M ESPE) or CAD/CAM lithium disilicate ceramic (LDC)(e.max, Ivoclar/Vivadent) overlay. After curing, the specimens were immediately placed in a prepared lymphocyte cell culture. Cytotoxicity was assessed using a dye exclusion method by simultaneous staining with ethidium bromide and acridine orange, aimed to determine percentages of viable, apoptotic and necrotic cells. Genotoxicity was studied using alkaline comet assay.ResultsFor Z100, the highest percentage of viable cells is recorded at T1 (93.7%) after direct light curing, followed by light curing through CRP (92.3%) and through LDC (91.7%T1,T3). For Filtek Supreme Ultra, the highest percentage of viable cells is recorded while curing through CRP (91.0% T2), followed by LDC (90% T1,T3) and direct light curing (88.7%T2).ConclusionFor both tested materials, preheating the procedure at T1 and T2 may be the procedure of choice. In terms of genotoxicity, preheating at T3 may not be suggested.

A study on current risk assessments and guidelines on the use of food animal products derived from cloned animals

The author widely surveyed and analyzed the food safety issues, ethical issues, permits, and approval of animal products from animals cloned by somatic cell nuclear transfer worldwide. As a result of a 2-year survey, the author found that there is no evidence that meat and milk derived from cloned animals or their progeny pose a risk to food safety in terms of genotoxicity, adverse reproductive effects, or allergic reactions. Most countries have not approved meat and milk derived from cloned animals, and their progeny are entering the food supply. To establish the guidelines, the author suggests four principles of safety assessment for meat and milk derived from cloned animals. The four main principles for safety assessment are similarities of chemical composition, adverse reproductive effects, genotoxicity, and allergic reactions under the influence of meat and milk from cloned animals and noncloned counterparts. This principle means that meat and milk derived from a cloned animal are safe if there are no differences in the four safety assessments of meat and milk between cloned animal's progeny and noncloned counterparts.

Molecular genetic and biochemical responses in human airway epithelial cell cultures exposed to titanium nanoparticles in vitro.

Titanium nanoparticles (NPs) have very wide application areas such as paint, cosmetics, pharmaceuticals, and biomedical applications. And, to translate these nanomaterials to the clinic and industrial domains, their safety needs to be verified, particularly in terms of genotoxicity and cytotoxicity. Therefore, in this study, we aimed to investigate of cytotoxicity and changes in gene expression profiles influenced by commonly titanium (as titanium carbide, titanium carbo-nitride, titanium (II) oxide, titanium (III) oxide, titanium (IV) oxide, titanium nitride, titanium silicon oxide) NPs in human alveolar epithelial (HPAEpiC) and pharynx (HPPC) cell lines in vitro since inhalation is an important pathway for exposure to these NPs. HPAEpiC and HPPC cells were treated with titanium (0-100 µg/mL), NPs for 24 and 48 h, and then cytotoxicity was detected by, [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT), uptake of neutral red (NR) and lactate dehydrogenase (LDH) release assays, while genotoxicity was also analyzed by cDNA array - RT-PCR assay. According to the results of MTT, NR and LDH assays, all tested NPs induced cytotoxicity on both HPAEpiC and HPPC cells in a time- and dose-dependent manner. Determining and analyzing the gene expression profiles of HPAEpiC and HPPC cells, titanium NPs showed more changes in genes related to DNA damage or repair, oxidative stress, and apoptosis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2056-2064, 2017.

Safety assessment of red-colored iron oxide as heavy metal lead pigment substitute in terms of genotoxicity in rat liver tissue

Lead is commonly used in battery, pipe and paint, and its exposure causes harmful effects on humans and animals. Especially, the usage of lead pigment-contained products increases frequency of lead exposure. Recently, to reduce frequency of the lead exposure, substitute for lead pigment were developed and used. However, the safety evaluation of substitute material is barely performed. In this study, we aimed to perform safety assessment of lead pigment substitute, red-colored iron oxide, compare to lead in terms of genotoxicity. To evaluate the safety of red-colored iron oxide, chemicals were orally administrated to rats for 28 days and genotoxic effect on the liver tissues was estimated using comet assay and micronucleus assay which have been recognized as standard genotoxicity testing guideline by Organization for Economic Co-operation and Development. Alkaline comet assay indicates DNA single strand and double strand break whereas micronucleus assay detects chromosomal damage. The result showed that red-colored iron oxide has lower genotoxicity than lead in the liver tissue. Through our study, we suggest that red-colored iron oxide pigment might have more safety than lead pigment and replace lead pigment. Further study assessing safety of red-colored iron oxide in other organs is needed.

Silikon Nanopartikül Maruziyetine Bağlı Olarak Oluşan İn Vitro Sitotoksik ve Moleküler Etkiler

Silicon nanoparticles are widely used for various applications including environmental, biological, chemical and physical. And, to translate these nanomaterials to the clinic and industrial domains, their safety needs to be verified, particularly in terms of genotoxicity and cytotoxicity. Therefore, in this study, we aimed to investigate of cytotoxicity and changes in gene expression profiles influenced by commonly silicon (as silicon carbide, silicon dioxide, silicon nitride) nanoparticles in human alveolar epithelial (HPAEpiC) and pharynx (HPPC) cell lines in vitro since inhalation is an important pathway for exposure to these nanoparticles. HPAEpiC and HPPC cells were treated with silicon (0-100 μg/mL), nanoparticles for 72 h, and then cytotoxicity was detected by, [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT) and lactate dehydrogenase (LDH) release assays, while genotoxicity was also analyzed by cDNA array - RT-PCR assay. According to the results of MTT and LDH assays, all tested nanoparticles induced cytotoxicity on both HPAEpiC and HPPC cells in dose-dependent manner. Determining and analyzing the gene expression profiles of HPAEpiC and HPPC cells, silicon nanoparticles showed changes in genes related to apoptosis, DNA damage or repair and oxidative stress. This study of gene expression profiles affected by nanotoxicity provides critical information for the clinical and environmental applications of silicon nanoparticles.

Is there a Genotoxic Potential of Endodontic Root Materials?

Leakage of components from endodontic materials (EM) can occur in case of apical extrusion into the periapical tissue. Therefore, an important prerequisite, besides the mechanical properties of the EM, is a high biocompatibility. In the present study, we elucidated the genotoxic potential of EMs of different base composition by utilizing the -H2AX assay. For investigation of the genotoxic potential of EM, supernatants of commercially available EM were prepared and dilutions were applied to human gingival fibroblasts. Non-toxic doses of EM were determined by cell viability assay. For the -H2AX assay, human gingival fibroblasts were incubated with predefined concentrations of the supernatants, which were found not to reduce cell viability. Hydrogen peroxide was utilized as positive control. Cells were fixed 1, 6 and 24 hours after addition of the supernatant to the medium, followed by immunostaining for -H2AX. For scoring of -H2AX foci, automated foci counting was performed in at least 80 cells per experiment and time point. The experiments were repeated at least twice. In contrast to hydrogen peroxide treated cells, no elevated -H2AX levels were detected in cells incubated with the EM supernatants. Samples treated with EM supernatants showed no elevated levels of -H2AX foci, e.g., no genotoxicity. Therefore, all types of EM seem to meet the standard to be called a biocompatible dental material in terms of genotoxicity, and, therefore, the application seems safe.