Genotoxicity In Human Lymphocytes Research Articles

Study of Chlorpheniramine-induced Genotoxicity in Human Peripheral Blood Lymphocytes

Background: Chlorpheniramine is an H1 receptor inverse agonist, which belongs to the first-generation class. It is generally regarded as a strong antihistamine with a wide variety of indications in allergic and non-allergic diseases. The extensive consumption of chlorpheniramine might culminate in less evident adverse effects, such as genotoxicity. Objectives: In this study, we attempted to assess the possible potential of chlorpheniramine in inducing genotoxicity. Methods: Human lymphocytes were separated into groups as follows: control group (Phosphate Buffered saline), Chlorpheniramine group (0.1, 0.5, 0.75, 1.5 mM), and Positive control group (cisplatin 0.4 µg/mL). After 24 hours of incubation, we conducted an alkaline comet assay to evaluate the DNA damage. Also, oxidative stress damage was evaluated by the levels of lipid peroxidation and glutathione oxidation. Results: Significant increases were observed in DNA percentage in tail and tail moment at high concentration (1.5mM, P<0.05). Likewise, at the same concentration, the MDA levels increased significantly in addition to the significant depletion in the level of glutathione. Conclusion: High concentration of chlorpheniramine significantly induced genotoxicity in human lymphocytes. In addition, we showed that oxidative stress was one of the mechanisms elaborated in chlorpheniramine genotoxicity at high concentrations.

Improvement of Phenolic Compound Extraction by Using Ion Exchange Chromatography and Evaluation of Biological Activities of Polyphenol-enriched Fraction of Rosa canina Fruits.

Rosa canina has been traditionally known as a medicinal plant. Different applications of fruits (Rose hip) comprise the food, perfume, and cosmetic industries. This study aimed to prepare an enriched polyphenolic fraction from Rosa canina in addition to its biological activities. Poly phenolic enriched fraction was prepared using Amberlite XAD-7 for removing unwanted components. Phenols, flavonoids, and anthocyanins content analyses showed that they increased significantly compared to the extract. HPLC analysis showed that this fraction is a rich source of ascorbic acid. The results of the DPPH, ferric-reducing antioxidant power (FRAP), ABTS, and nitric oxide assay confirmed that the antioxidant activities of the fraction had been increased compared to the extract. The oxygen radical absorbance capacity (ORAC) assay and cellular antioxidant activity of the fraction also confirmed its potential antioxidant activity. This fraction showed xanthine oxidase inhibitory activity at 100 µg/mL concentration. Comet assay analysis revealed that this fraction at 25 - 100 µg/mL concentrations inhibited H2O2 genotoxicity in human lymphocytes. This study suggests that the fruit of Rosa canina could be considered as a potential antioxidant, a xanthine oxidase inhibitor, and an antigenotoxic source, and the application of Amberlite XAD-7 improves extraction efficiencies through enrichment of phenolic compounds in this plant.

The Alleviating Effect of Herniarin Against Ionizing Radiation-Induced Genotoxicity and Cytotoxicity in Human Peripheral Blood Lymphocytes.

Herniarin is a simple coumarin that is found naturally in some plant species. In this study, we aimed to evaluate the protective effect of herniarin against ionizing radiation-induced genotoxicity and cytotoxicity in human peripheral blood lymphocytes. Herniarin was added to human lymphocytes before irradiation with a dose of 2 Gy of Xrays. The antagonistic potential of herniarin against radiation was measured by MTT [3-(4,5- dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide] assay, micronucleus assay, flow cytometry, and reactive oxygen species (ROS) level analysis. The maximum survival of lymphocytes against radiation was observed at a concentration of 50 μM of herniarin and a treatment time of 1 h. Pretreatment with 50 μM herniarin significantly decreased the micronuclei frequency, the percentage of apoptotic lymphocytes, and the ROS level in irradiated human lymphocytes. Moreover, 50 μM herniarin significantly increased the cytokinesis blocked proliferation index in irradiated lymphocytes. Herniarin could reduce radiation-induced cytotoxicity and genotoxicity in human lymphocytes. To complete the results of this study, it is suggested that in the future, more preclinical studies with larger samples or animal models be performed on herniarin.

The effect of Anzer honey on X-ray induced genotoxicity in human lymphocytes: An in vitro study.

Anzer honey is well known in Turkey and used for its medicinal properties, especially for pharyngitis, tonsillitis, ulcers and cancer. In this study, we investigated whether Anzer honey, which is shown to have antioxidant, anti-tumoral, and anti-inflammatory properties, has a protective effect against X-ray induced genotoxic damage by cytogenetic methods. Peripheral blood lymphocytes isolated from 20 healthy volunteers were divided into two groups and cultivated by conventional methods. Study group lymphocytes were treated with 10% diluted honey while those in the control group were not. Both groups were exposed to a high dose (2 Gy) X-ray at the 48th hour of culture. Conventional cytogenetic staining and Giemsa banding methods were applied to evaluate chromosomal breakage and ring formation. Micronucleus frequencies were determined by the cytokinesis-block micronucleus (CBMN) assay. Paired sample t test was used to compare groups. Anzer honey, which was analyzed melissopalynologically, was used. Micronucleus frequency was significantly decreased in the study group (CI=348.75 ± 31, median 326, min. 98, max. 704) compared to the control group (CI=489.10 ± 27, median 500, min. 216, max. 645) (p=.001). Chromosomal breakage was also significantly decreased in the study group (CI=118.70 ± 16, median 109, min. 12, max. 316) compared to the control group (CI=233.60± 25, median 225, min. 65, max. 492) (p < .0001). This is the first study indicating that genotoxic damage in the peripheral blood lymphocytes of healthy volunteers induced by X-radiation may be prevented or alleviated by adding Anzer honey in vitro. These results encourage further research about the protective effects of honey. RESEARCH HIGHLIGHTS: Anzer honey has a genoprotective effect against radiation-induced genotoxicity, probably by preventing oxidation damage.

Imine resveratrol analogs (IRAs): The strong antioxidant that can protect lymphocytes from oxidative damage.

Imine resveratrol analogs (IRAs) are promising new agents that can have higher positive effects and, simultaneously, lower negative properties than resveratrol. In this study,three imine hydroxy derivatives (2-((4-hydroxyphenylimino) methyl) phenol [IRA1], 3-((4-hydroxyphenylimino) methyl) phenol [IRA2], and 4-((4-hydroxyphenylimino) methyl) phenol [IRA3]) were prepared and tested in several biological assays. They performed superior to resveratrol in several antioxidant and biological assays, showing high antioxidant capacity and low genotoxicity. Ferric reducing antioxidant power assay (FRAP) and hydroxyl radicals scavenging assay revealed good Fe3+ to Fe2+ reduction and strong inhibition of hydroxyl radical formation, respectively. High dosage (1 mmol/dm3 ) of IRA2 and IRA3 did not cause genotoxicity in human lymphocytes. Moreover, lymphocytes pretreated with all three IRAs accumulated only very few DNA breaks induced by H2 O2 than lymphocytes pretreated with resveratrol. Additionally, the number of detected DNA breaks appearing after removal of damaged DNA bases, 8-oxo-7,8-dihydroguanine (8-oxoG), did not dramatically increase in lymphocytes treated with IRA2. Thus, we concluded that IRAs, especially IRA2, are strong antioxidants with the ability to protect lymphocytes from oxidative damage.

In vitro effects of Sunset Yellow on Chromosomal Damage and Sister Chromatid Exchanges in Human Peripheral Lymphocytes

Sunset Yellow (SY) is an organic azo dye that is used extensively as a coloring agent in many industries, such as cosmetics, pharmaceuticals ,and foodstuffs. Many studies have conflicting results about the genotoxicity effect of SY. Thus, the purpose of this study was to provide additional data concerning SY genotoxicity in human lymphocytes by using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) assay. Four concentrations of Sunset Yellow (1, 5, 20 ,and 50 mg/ml) were used on human lymphocyte cultures. Positive and negative controls were mitomycin C and distilled water, respectively. Compared to the control, SY caused a significant increase in CAs and SCEs frequencies at all concentrations. A total of five types of CAs were observed, such as gaps, fragments, RCF, stickiness,and polyploidy. According to the present results, high concentrations of SY are genotoxic in vitro to cultured human lymphocytes. To determine its full genotoxicity potential, SY should be tested in other test systems.

Restoration and stabilization of acrylamide-induced DNA, mitochondrial damages and oxidative stress by chrysin in human lymphocyte

ABSTRACT Background Acrylamide (AA) is a water-soluble toxic chemical that is considered one of the most important food contaminants. Furthermore, AA is considered a major public health risk. Methods This study was designed to evaluate the effects of AA on cytotoxicity, oxidative damage and genotoxicity in human lymphocytes and also to evaluate the protective effects of the chrysin (CH). Lymphocytes after isolation from the blood were treated with AA (50 µM), AA (50 µM) plus CH (10, 25, 50 µM) and CH (50 µM), and parameters such as cell viability, mitochondrial and lysosomal damage, as well as oxidative damage to DNA were examined. Results The results showed that CH was able to reduce cytotoxicity, reactive oxygen species (ROS) levels, lipid peroxidation (LPO) level, collapse in mitochondrial membrane potential (MMP) and oxidative damage of DNA caused by AA in human lymphocytes. Also, co-treatment of the AA-exposed human lymphocytes with CH increases the glutathione (GSH) levels. Conclusion Results suggest that CH (10, 25, 50 µM) shows a protective role in AA-induced cytotoxicity, oxidative stress, mitochondrial damage and DNA oxidative damage.

Potassium Sorbate Induces Oxidative Stress and Genotoxicity in Human Lymphocytes

Potassium sorbate, a potassium salt of sorbic acid, has been used as food preservative and antimicrobial agent.Some observations in rat and hamster cells suggest its toxicity. However, observations in human cells arelimiting. Therefore, it has been intended to investigate impacts of potassium sorbate on human lymphocytes.The lymphocytes were cultured and treated with 0.5, 1.0, 1.5 and 2.0 mg/ml of potassium sorbate for 24 and48 h. Evaluations of its impacts were done through the MTT assay, analysis of chromosomal aberrations,formation of micronucleus and activities of superoxide dismutase. The results revealed that potassiumsorbate induced oxidative stress, genotoxicity, damages to chromosome, formation of micronucleus inhuman lymphocytes.

Vitamin E protects against cisplatin-induced genotoxicity in human lymphocytes

Cisplatin is an anticancer drug that is widely used in treatments of human malignancies such as ovaries,’ testes,’ and solid tumors of the head and neck. However, the use of cisplatin in the treatments can be associated with DNA damage and high risk to the development of secondary malignancies. Vitamin E is a strong lipophilic antioxidant that has the ability to protect normal cells from chromosomal damage and promote the repair of the damaged DNA. In the current study, the possible protective effect of vitamin E on DNA damage induced by cisplatin was investigated. For that, chromosomal aberrations (CAs) frequency and the number of sister chromatid exchanges (SCEs) were measured in cultured human lymphocytes. Results showed that cisplatin statistically significant increases in the number of cells with CAs (P < 0.05) and in the frequency of SCEs (P < 0.05) as compared to the control group. These increases were significantly lowered by pretreatment of cells with vitamin E. Additionally, cisplatin reduced mitotic index at used concentrations (P < 0.05), which was normalized by vitamin E. Therefore, we conclude that vitamin E can prevent the genotoxicity of cisplatin on cultured human lymphocyte.

Poly(dimethylsiloxane) Induces Cytotoxicity and Genotoxicity in Human Lymphocytes

Poly-(dimethylsiloxane) (PDMS) is extensively used in edible fats and oils as an antifoaming agent. However, in vitro cyto-genotoxicity analyses of PDMS in primary human cells are limited. The present study was performed as a safety assessment encompassing the cytotoxicity and genotoxicity of PDMS on human peripheral blood lymphocytes. Isolated lymphocytes were exposed to different concentrations of PDMS from 0 to 20 mg/l at 37 °C for up to 24 h. Our results suggest a significant dose-dependent decline in cell viability at concentrations 2.5 mg/l and above as estimated by trypan blue dye exclusion test and MTT assay. The IC-50 of PDMS was found to be 20 mg/l after 24 h incubation. Moreover, a significant genotoxicity were observed at 2.5 mg/l and above as assessed by comet and DNA diffusion assays. Hence, consumption of PDMS may not be safe at concentrations above 2.5 mg/l. Further studies are needed to establish its in vivo cyto-genotoxicity mechanisms.

In Vitro Study Towards Role of Acrylamide-Induced Genotoxicity in Human Lymphocytes and the Protective Effect of L- Carnitine

ABSTRACT Acrylamide (AA), is an important industrial compound, formed during food processing under high temperature. Due to its potential carcinogenic effect, it has been recognized as a human health concern. In this study, we investigated the role of oxidative stress in acrylamide’s genotoxicity and protective role of L- carnitine (LCA) in human lymphocytes. The micronucleus test (MNT) was used to monitor AA genotoxicity after 20h exposure to concentrations of 0.25,50 and 100 mM. Furthermore we evaluated oxidative stress markers, such as reactive oxygen species (ROS), lipid peroxidation (LPO) and glutathione (GSH) content. In MNT, It has been found that AA at high concentrations (50 and 100 µM) significantly increased the micronuclei (MN) frequencies. On the one hand, AA exposure induced ROS formation, LPO and also GSH oxidation in treated lymphocytes. On the other hand, pretreatment with LCA (100 and 200µM) inhibited AA-induced oxidative stress which subsequently led to decreasing of the micronuclei (MN) frequencies in human lymphocytes. In overall, the clastugenic effect of acrylamide was confirmed. Also, it has been observed that LCA prevented AA genotoxicity via amelioration of oxidative stress in human lymphocytes. Therefore, oxidative stress suggested as an important factor involved in acrylamide-induced genotoxicity.

Neonikotinoidler ile İnsan Lenfositlerinde Genotoksisitenin Uyarılması

Bu çalışmada, neonikotinoid grubu&#x0D; insektisitlerden imidakloprid (İMİ) ve asetamiprid (ASE)’in genotoksik etkileri&#x0D; insane peripheral lenfosit&#x0D; hücrelerinde Kardeş Kromatid Değişim&#x0D; Testi (KKD) ile araştırılmıştır. Bu maddelerin olası genotoksik etkilerinin&#x0D; giderilebilmesi için de Portulaca oleracea&#x0D; L. (Semizotu) bitkisine ait su ve methanol ekstreleri kullanılmıştır. İnsektisitlere&#x0D; ait genotoksisitenin belirlenmesi amacıyla kültür ortamına farklı konsantrasyonlarda&#x0D; İMİ (50, 100, 250 ve 500 ppm) ve ASE (25, 50, 100 ve 250 ppm) insektisitleri ilave&#x0D; edilmiştir.Yapılan incelemeler sonucu, her iki insektisitin artan konsantrasyonuna&#x0D; bağlı olarak tüm uygulama gruplarında KKD frekansında artış gözlenmiştir&#x0D; (P&amp;lt;0,05). Ancak semizotu bitkisinin su (POsu) ve methanol (POmet)&#x0D; ekstreleri, insektisitlerin en yüksek uygulama grupları (İMİ:500ppm ve ASE:250ppm)&#x0D; ile birlikte (1:1/v:v) uygulandığı zaman KKD frekansının azaldığı ve bunun da&#x0D; istatistiksel olarak önemli olduğu bulunmuştur (P&amp;lt;0,05). Elde edilen bu bulgulara göre kardeş&#x0D; kromatit değişiminde gözlenen artış, genetik materyalde oluşan hasarın&#x0D; bir göstergesi olarak değerlendirilmiştir. Ayrıca POmet ve POsu&#x0D; ile bu hasarların azaltılması da semizotunun antigenotoksik bir ajan&#x0D; olabileceğini göstermektedir.

Genotoxic and Antigenotoxic Activities of Thai Bee Pollen and Its Extracts in Human Lymphocytes by in Vitro Sister Chromatid Exchange Assay

Bee pollen has been used as a food supplement and as a traditional medicine for thousands of years. Our study demonstrated that by in vitro sister chromatid exchange assay, Mimosa pudica crude bee pollen extract (0.005-5.0 μg/mL CE) from Chiangmai, Northern Thailand, increased genotoxicity in human lymphocytes at concentrations of 0.005 and 0.5 μg/mL by 20% and 24% respectively, compared to the RPMI control. Its defatted extract (DE) at 0.005-5.0 μg/mL increased the activities by 24–32% whereas the lipid extract (LE) at 0.00125 μg/mL but not at 0.0125–1.25 μg/mL increased the activities by 25%. Only CE at 5.0 μg/mL induced cytotoxicity. Pretreatments of CE, DE, and LE at 0.5, 5, and 0.00125 μg/mL induced antigenotoxicities against doxorubicin, a potent genotoxic chemotherapeutic agent by 24%, 28%, and 16%, respectively. Their protective mechanisms are feasibly involved with α-tocopherol and phenolic contents such as gallic acid and ferulic acid.

In vitro and in vivo antileishmanial activity of Artemisia annua L. leaf powder and its potential usefulness in the treatment of uncomplicated cutaneous leishmaniasis in humans

Cutaneous leishmaniasis (CL) is a tropical disease that affects millions of individuals worldwide. The current drugs for CL may be effective but have serious side effects; hence, alternatives are urgently needed. Although plant-derived materials are used for the treatment of various diseases in 80% of the global population, the validation of these products is essential. Gelatin capsules containing dried Artemisia annua leaf powder were recently developed as a new herbal formulation (totum) for the oral treatment of malaria and other parasitic diseases. Here, we aimed to determine the usefulness of A. annua gel capsules in CL. The antileishmanial activity and cytotoxicity of A. annua L. capsules was determined via in vitro and in vivo studies. Moreover, a preliminary evaluation of its therapeutic potential as antileishmanial treatment in humans was conducted in 2 patients with uncomplicated CL. Artemisia annua capsules showed moderate in vitro activity in amastigotes of Leishmania (Viannia) panamensis; no cytotoxicity in U-937 macrophages or genotoxicity in human lymphocytes was observed. Five of 6 (83.3%) hamsters treated with A. annua capsules (500mg/kg/day) for 30 days were cured, and the 2 examined patients were cured 45 days after initiation of treatment with 30g of A. annua capsules, without any adverse reactions. Both patients remained disease-free 26 and 24 months after treatment completion. Capsules of A. annua L. represent an effective treatment for uncomplicated CL, although further randomized controlled trials are needed to validate its efficacy and safety.

Impact of Anthocyanidins on Mitoxantrone-Induced Cytotoxicity and Genotoxicity: An In Vitro and In Vivo Analysis.

Hypothesis. Anthocyanins possess well-known biological effects and suppress DNA damage induced by therapeutic topoisomerase poisons. Our study focusses on the modulatory effects of anthocyanidins—malvidin (MAL) and pelargonidin (PEL)—on topoisomerase II poison mitoxantrone (MXT)-induced cytotoxicity and genotoxicity in in vitro and in vivo conditions. Study design. HepG2 cells were treated with MXT (1-10 µM), MAL (10-100 µM,) and PEL (5-640 µM) to determine cell viability. Further, experiments on cytotoxicity and apoptosis induction by single agents or combinations were performed. In vitro and in vivo antigenotoxic effect of MAL/PEL against MXT was evaluated in human lymphocytes and mouse bone marrow cells. Methods. Cytotoxicity of test agents and apoptosis induction in HepG2 cells was assessed by MTT assay, trypan blue dye exclusion assay and Hoechst 33258 staining. Antigenotoxic effects of MAL/PEL against MXT were assessed in co-treated human lymphocytes and bone marrow from mice that received MXT intraperitoneally 30 minutes post MAL/PEL oral administration Results. Dose-dependent cytotoxicity was observed with all 3 test agents in HepG2 cells. Highest test concentration of 100 µM MAL, 640 µM PEL, and 10 µM MXT decreased HepG2 cell viability by 80%, 30%, and 90%, respectively. The combination of 1 µM MXT + 80 µM MAL reduced cell viability better than single agents. MAL/PEL treatment significantly reduced MXT-induced genotoxicity in human lymphocytes and micronuclei formation in mice. Conclusion. Combination of MAL/PEL with lower doses of MXT, especially MAL+MXT increases the cytotoxicity in cancer cells. In addition, MXT treatment with MAL/PEL reduced MXT-induced genotoxicity and protected normal cells during chemotherapy.

Boron Compounds Counteracts Oxidative Stress Mediated Genotoxicity Induced by Fe&lt;sub&gt;3&lt;/sub&gt;O&lt;sub&gt;4&lt;/sub&gt; Nanoparticles &lt;i&gt;In Vitro&lt;/i&gt;

Due to rapid growing of nanotechnology, it is currently being used in many areas including biotechnology, electronics, drug delivery systems, cosmetics, material science and biosensors. Oxidative stress is considered as main cause behind the toxicity of nanoparticles (NPs). Recent reports indicate that boron is effective in protecting cells or organisms against oxidative damages by enhancing antioxidant defense mechanisms. However, protective role of boron compounds in nanotoxicity is not investigated yet. Therefore we assessed the potential protective role of boric acid (BA) and borax (BX) against the toxic responses of nano-Fe3O4 particles (IO NPs) in cultured human whole blood cells. Our results showed that IO NPs induced genotoxicity in human lymphocytes demonstrated by sister chromatid exchange (SCE) and 8-hydroxy-2′-deoxyguanosine (8-OH-dG) assays. Again, IO NPs caused decreases of total antioxidant capacity (TAC) and decreases of total oxidative stress (TOS) levels in vitro. Co-application of boric acid and borax (2.5 to 10 ppm) into the cell cultures significantly ameliorated genotoxicity and oxidative stress caused by IO NPs. In a conclusion, this study is the first report revealing that BA and BX significantly protected human blood cells from the toxicity of IO NPs, which is mediated through the generation of oxidative stress and depletion of antioxidant capacity.

Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes.

Following one of the world’s largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM), a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN) and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 μL/mL), the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 μg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes.

Protective effects of Dioscorea membranacea rhizome ethanolic extract against doxorubicin-induced genotoxicity in human lymphocytes in vitro

Dioscorea membranacea rhizome is commonly used as an ingredient in traditional Thai remedies for inflammatory diseases and cancers. Our previous study reported that the ethanolic extract of Dioscorea membranacea rhizome (EEDM) was selectively cytotoxic to lung and breast cancer cell lines [1]. However, the underlying mechanisms of its action are still unclear. One possible mechanism might be their anti-genotoxic activities. To investigate the anti-genotoxic potential of the EEDM, in vitro chromosome aberration assay was conducted, testing EEDM against doxorubicin (DXR), a potent genotoxic compound. Genotoxicity indicated by chromatid-type and chromosome-type aberrations and cytotoxicity as shown by mitotic index were analyzed. Human lymphocytes were pretreated with various concentrations of EEDM (0.005 – 50 ng/ml) followed by 0.1 µg/mL DXR. Plain RPMI and DXR were used as negative and positive controls, respectively. The results demonstrated that EEDM pretreatment at 0.5 ng/ml significantly decreased DXR-induced chromatid-type aberrations by a factor of 4.8. Other EEDM pretreatments at 0.05 and 5 ng/ml also tended to decrease DXR-induced chromatid-type aberrations, although they were not statistically significant. Chromosome-type aberration and cytotoxicity was not detected at all EEDM pretreatments. The outcomes revealed that in vitro EEDM pretreatment at a specific dose has anti-genotoxic properties against genotoxic hazards such as DXR in human cells. Therefore, EEDM might be useful not only for anti-cancer treatment but also for cancer prevention. Further in vivo anti-genotoxic studies are needed to confirm this in vitro results.

Radioprotective effect of mefenamic acid against radiation-induced genotoxicity in human lymphocytes.

PurposeMefenamic acid (MEF) as a non-steroidal anti-inflammatory drug is used as a medication for relieving of pain and inflammation. Radiation-induced inflammation process is involved in DNA damage and cell death. In this study, the radioprotective effect of MEF was investigated against genotoxicity induced by ionizing radiation in human blood lymphocytes.Materials and MethodsPeripheral blood samples were collected from human volunteers and incubated with MEF at different concentrations (5, 10, 50, or 100 µM) for two hours. The whole blood was exposed to ionizing radiation at a dose 1.5 Gy. Lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis blocked binucleated lymphocyte.ResultsA significant decreasing in the frequency of micronuclei was observed in human lymphocytes irradiated with MEF as compared to irradiated lymphocytes without MEF. The maximum decreasing in frequency of micronuclei was observed at 100 µM of MEF (38% decrease), providing maximal protection against ionizing radiation.ConclusionThe radioprotective effect of MEF is probably related to anti-inflammatory property of MEF on human lymphocytes.

Evaluation of cytotoxic and antimicrobial effects of two Bt Cry proteins on a GMO safety perspective.

Studies have contested the innocuousness of Bacillus thuringiensis (Bt) Cry proteins to mammalian cells as well as to mammals microbiota. Thus, this study aimed to evaluate the cytotoxic and antimicrobial effects of two Cry proteins, Cry8Ka5 (a novel mutant protein) and Cry1Ac (a widely distributed protein in GM crops). Evaluation of cyto- and genotoxicity in human lymphocytes was performed as well as hemolytic activity coupled with cellular membrane topography analysis in mammal erythrocytes. Effects of Cry8Ka5 and Cry1Ac upon Artemia sp. nauplii and upon bacteria and yeast growth were assessed. The toxins caused no significant effects on the viability (IC50 > 1,000 µg/mL) or to the cellular DNA integrity of lymphocytes (no effects at 1,000 µg/mL). The Cry8Ka5 and Cry1Ac proteins did not cause severe damage to erythrocytes, neither with hemolysis (IC50 > 1,000 µg/mL) nor with alterations in the membrane. Likewise, the Cry8Ka5 and Cry1Ac proteins presented high LC50 (755.11 and >1,000 µg/mL, resp.) on the brine shrimp lethality assay and showed no growth inhibition of the microorganisms tested (MIC > 1,000 µg/mL). This study contributed with valuable information on the effects of Cry8Ka5 and Cry1Ac proteins on nontarget organisms, which reinforce their potential for safe biotechnological applications.