جستجوی مقالات مرتبط با کلیدواژه « genotoxicity » در نشریات گروه « پزشکی »

The beetroot extract has long been widely used in the food industry. However, information on its genetic safety is insufficient. In addition, there is evidence to suggest its potential beneficial health effects. The aim of this study was to evaluate the genotoxic and antigenotoxic potentials of red beetroot extract in rats.

The endpoints analyzed were chromosomal aberrations in bone marrow cells and DNA damage in peripheral blood, liver, kidneys, and gastrointestinal tract cells assessed using the alkaline comet assay.

There were no statistically significant differences between the analyzed data from the negative control and those of the groups treated with doses of beetroot extract up to 2000 mg/kg for both of the study endpoints. The findings demonstrated the absence of genotoxicity. The comet assay revealed considerable antigenotoxicity of the beetroot extract (5-100 mg/kg) in the liver, stomach, duodenum, and rectum versus the effects of methyl methanesulfonate and dioxidine mutagens with different mechanisms of action. No anticlastogenic activities were detected in the bone marrow cells while observing the protective effects on blood cells, indicating the tissue specificity for beetroot extract antigenotoxicity.

Based on the study findings, the beetroot extract meets the basic requirements for being a chemopreventive agent. The advantages are low cost, practicality of use, efficacy, and safety. Moreover, this agent may be used to develop food products with chemopreventive properties.

Lambda-cyhalothrin (LCT) belongs to pyrethroid insecticides, the use of which has increased for pest control. It is essential to study the effects of LCT on the DNA of living organisms to prevent its mutagenic and carcinogenic properties. Currently, there is a lack of information on the effects of LCT on humans. This study examined the cytotoxicity and genotoxicity of LCT insecticides on human dental pulp stem cells (DPSCs).

We examined the cytotoxicity of LCT at serial concentrations of 0.5, 1, 2.5, 5, 10, 25, and 50 µM using an MTT assay. Four concentrations of LCT at 0.5, 1, 25, and 50 µM were selected from the cytotoxicity curve and subjected to a comet assay to assess genotoxicity.

The results of the MTT assay showed that LCT inhibited cell proliferation at 1 µM concentration of the 5% formulation, while the other concentrations of LCT at 0.5, 2.5, 5, 10, 25, and 50 µM increased cell proliferation rates by 10, 1, 4, 20, 59, and 76%, respectively. The results of the comet assay provided evidence that the LCT insecticide induced a statistically significant increase in DNA damage in DPSCs at all tested concentrations compared to those of the negative controls (P>0.05).

The LCT insecticide was genotoxic to DPSCs but was not cytotoxic at the tested concentrations, except at 1 μM. Instead, it increased cell proliferation. This suggests that LCT may function through an additional mechanism that mimics that of estrogen and may potentially become a candidate as a xenoestrogen.

Hydroxychloroquine (HCQ) is a drug used to treat malarial parasites and it was extensively used during the initial phase of COVID-19. However, HCQ demonstrated certain serious effects when administered to patients. Hence, this study intends to determine its toxicity by exposing it to human peripheral blood and the fly model. In the present experimental study, HCQ (200 mg) was tested in different volumes (62.5 μl - 500 μl) on human blood samples (in vitro) and Drosophila melanogaster (in vivo). Hemolytic assay, trypan blue assay, mitotic index, chromosomal aberration, and DNA fragmentation assay were used to assess the sublethal effects of HCQ. The results implied that HCQ, at its highest concentration (500 μl), showed maximum lysis in the hemolytic assay, and an increased number of dead cells were observed with increasing concentration in trypan blue assay. Also, the percent mitotic index decreased with increasing concentration of HCQ. Chromosomal aberrations, including breaks, centromeric disruption, dicentrics, and pulverized chromosomes, were observed on exposure to HCQ. The number of fragments in agarose gel electrophoresis revealed damage to DNA. Therefore, these results provide evidence and prove the cytotoxicity and genotoxicity of HCQ. HCQ is found to have cytotoxic and genotoxic effects. These results imply that further examinations must be conducted before prescribing HCQ to treat various diseases.

The number of micronuclei in oral exfoliated buccal mucosal cells of analog (basic) and smart mobile phone users was evaluated and compared.

The study population constituted 30 individuals using basic and smartphones within the age group of 45–55 years. They were divided into two groups: Group 1–15 participants using basic mobile phones and Group 2–15 participants using smart mobile phones. Exfoliated buccal mucosal cells were collected from both right and left buccal mucosa, stained with Papanicolaou stain, and evaluated microscopically for the estimation of micronuclei count. Mean micronuclei count was compared statistically between the study groups and also between the sides of frequent usage and opposite sides within the study groups.

There was a significant increase in the mean micronuclei count in Group 2 compared to Group 1 and the comparison of mean micronuclei count between the side of frequent phone usage (right side) and opposite side (left side) also showed significant difference in both Groups 1 and 2.

Despite technological advance and high‑end features, the use of smartphones causes more genotoxicity compared to basic model or analog phones. Although this technology‑dominated era mandates use of such phones as a part of routine lifestyle, it is imperative to adopt safety precautions such as use of headphones while talking, carrying a separate pouch for mobile phones to minimize the genotoxic damage.

 Indomethacin is one of the most widely used non-steroidal anti-inflammatory drugs. This study aimed to investigate the protective effects of curcumin against indomethacin-induced genotoxicity.

Experimental approach:

 For in vitro studies, human peripheral blood lymphocytes were obtained from a healthy volunteer and treated for 24 h as follows: vehicle control, indomethacin at 100 and 200 μM, indomethacin (100 μM and 200 μM) plus curcumin (27 μM). For in vivo experiments, mice received a single i.p dose of curcumin (100 mg/kg) and after 30 min genotoxicity induction was carried out by a single   i.p injection of indomethacin at 10, 20, and 40 mg/kg. After 24 h, bone marrow cells were obtained from mice femurs. Genotoxicity was evaluated using a micronucleus assay. Oxidative damage was also inspected both  in vitro and in vivo.

 In-vitro studies indicated that co-treatment with curcumin caused a significant decrease in the average micronuclei percentage and MDA level, and a significant increase in GSH concentration compared to the groups treated only with indomethacin. In-vivo findings revealed that pretreatment with curcumin induced a significant increase in the average ratio of polychromatic erythrocyte/normochromic erythrocyte, GSH concentration and caused a significant decrease in the average percentage of micronuclei and MDA level, in comparison with the group treated only with indomethacin.

Conclusion and implications:

 Curcumin attenuated indomethacin-induced genotoxicity both in vitro and  in vivo. These effects might be partially exerted by decreasing oxidative stress. Further studies are required to elucidate the exact genoprotective mechanism of curcumin against indomethacin.

Formaldehyde is an irritating substance that is categorized as a definite carcinogen (Group A1), according to the International Agency for Research on Cancer (IARC). This study was conducted to determine the role of this substance in the frequency of micronuclei (MN) in the buccal mucosal cells due to long-term exposure of the pathology staff to formaldehyde.

In this case-control study, 32 pathology laboratory staff members were assigned to the case group, and 32 staff members who were not exposed to formaldehyde were assigned to the control group. Buccal mucosa cells were collected with a wet spatula and stained with Papanicolaou stain. In each sample, 500 cells were counted; then, the frequency of MN and the average number of MN in the micronucleated cells were assessed and compared between the 2 groups using the independent t test. Furthermore, the relationship between gender and MN was evaluated using the independent t test. The relationship between years of exposure and time of exposure during the day (in hours) for the case group, as well as the relationship between age and frequency of MN was analyzed using the Pearson correlation coefficient.

The mean frequency of MN in exfoliated buccal cells was 18.33±12.36 in the case group, which was significantly higher than the control group (10.55±6.22; P=0.003). The difference in the mean number of total MN in the micronucleated cells was not significant between the case and control groups (P=0.11). The relationship between sex, age, and years of exposure with the mean frequency of MN and the total number of MN in the micronucleated cells was not significant. The relationship between exposure time during the day and both the mean frequency of MN and the total number of MN in the micronucleated cells was significant (P=0.03).  

Formaldehyde exposure and extended time of exposure during the day can increase the frequency of MN, which can prognosticate the incidence of precancerous and cancerous lesions. Therefore, continuous exposure to formaldehyde can be considered an occupational health hazard, though further studies are needed to confirm this result.

The present study aims to investigate the role of breast cancer-susceptibility gene 1 (BRCA1) protein in the β-Glucan (βG) molecule mediated regulation of lipopolysaccharide (LPS)-induced liver genotoxicity.

In this experimental study, totally, 32 male Swiss Albino mice were randomly divided into 4 equal groups: control (C), LPS-administered (LPS), βG-administered (βG) and βG-pre-administered/LPS-administered (βG+LPS). The βG was injected at the dose of 150 mg/kg/day intraperitoneally (i.p.) for 3 days. A single dose of 4 mg/ kg (i.p.) LPS was administered 24 hours after the last βG injection. BRCA1 expression was determined by western blot analysis and confirmed by quantitative immunofluorescence. Proliferating cell nuclear antigen (PCNA), nuclear factor erythroid 2–related factor (Nrf2) and 8-OHdG protein levels were also determined by the immunofluorescence analysis. The alkaline comet assay was performed. superoxide dismutase (SOD), catalase (CAT) and membrane lipid peroxidation were biochemically measured, and light microscopic histology was evaluated.

The BRCA1 expression level was significantly decreased in the LPS group. However, in the βG+LPS group, expression of BRCA1 protein was over 2 folds higher than the control. After the LPS induction, the DNA strand breaks, oxidative DNA lesions and abnormal proliferation of the liver cells were almost entirely suppressed in βG preadministrated animals, indicating the BRCA1 mediated ubiquitination of PCNA and activation of the DNA damage repair pathways. Activation of Nrf2 in the βG+LPS group resulted in an increase in the levels of Nrf2 pathway dependent antioxidant enzymes SOD and CAT, prevented the peroxidation of membrane lipids and maintained the histological architecture of the liver.

The results manifested that the βG is a strong inducer of the BRCA1 protein expression in the LPSinduced hepatic stress and the protein constitutes the key component of a βG mediated liver protection against an LPS-induced genotoxic and pathological damage.

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.

In this study, we attempted to assess the possible potential of chlorpheniramine in inducing genotoxicity. 

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.

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.

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.

Statement of the Problem: 

Mobile usage has increased worldwide over the past two decades. There are conflicting reports about the carcinogenic effects of cell phone radiation on the oral mucosa. Micronucleus (MN) is considered a reliable marker for genotoxic damage.

This study aimed to identify the impact of mobile phone radiation on the MN frequency in oral mucosal cells.

In this descriptive-analytical study, 50 mobile phone users between the age group of 20–38 years were included. Samples were obtained from the right and left cheek mucosa of each subject (a total 100 cell samples). Every participant filled out a questionnaire about his or her cell phone usage habits. Additionally, personal information such as age, gender, and body mass index (BMI) were assessed. The Feulgen and Papanicolaou staining methods were used for staining of the cell samples. A total of 1000 cells in each sample were evaluated for MNs.

The mean number of MN in exposed and non-exposed mucosa by Feulgen method was 0.71±1.13 and 0.57±1.36, respectively. Also in Papanicolaou staining, the mean number of MN in the exposed mucosa and non-exposed mucosa was 6.94±6.61 and 6.54±6.88, respectively, but these differences were not significant (p> 0.05). The frequency of MN in non-specific DNA staining was significantly (5- to 6-fold) higher than DNA-specific staining. We observed no statically significant differences between MN frequency according to age, gender, BMI, and other cell phone usage habits (p> 0.05).

This study showed that cell phone use does not cause genotoxic effects in the buccal mucosa in the oral cavity. Moreover, using non-specific DNA staining methods can increase the frequency of MN by more than 5- to 6-fold.

Cone beam computed tomography (CBCT) is considered a common examination for dentistry problems. Cellular biology can be affected by exposure to ionizing radiations procedures. In this study, we aimed to assess the genotoxicity and cytotoxicity effects of CBCT dental examinations at two different fields of view (FOVs) in exfoliated buccal epithelial cells.

Sixty healthy adults participated in the current study. They were divided into two identical groups; CBCT with FOV of 6*6 cm2 and 8*11 cm2. Exfoliated oral mucosa cells were prepared immediately before and after 10-12 days of CBCT exposure. The cytological smears were stained with the Papanicolaou technique. The amounts of micronuclei and other cytotoxicity cellular changes (Pyknosis, Karyolysis, and Karyorrhexis) were evaluated. The variables of the parameters before and after CBCT examination in the two investigated FOVs were performed using Wilcoxon test and paired-samples t-test in SPSS software.

The micronuclei and other cytotoxic changes parameters before and after CBCT exposure for both FOVs (6*6 and 8*11 cm2) increased significantly (p<0.001). Furthermore, a significant difference (p<0.05) was observed between the investigated parameters at the two FOVs. Notably, the FOV of 8*11 cm2 had more side effects than that of 6*6 cm2. There were no statistically significant among males and females for both FOVs.

CBCT examinations of dental disorders would increase the risks of inducing genetic damage. The cytotoxicity and chromosomal damage were considered in males and females in both investigated FOVs (6*6 and 8*11 cm2). In this regard, the use of CBCT must be following the ALARA principle.

Osthole, a plant-derived coumarin, has shown numerous pharmacological effects. However, its genoprotective effects against cadmium-induced DNA damage have not been determined yet. Therefore, this project aimed to assess the effectiveness of osthole against genotoxicity caused by cadmium.

Experimental approach:

 For this purpose, human umbilical vein endothelial cells (HUVECs) were incubated with various concentrations of osthole (40, 60, 80, and 120 µM) 24 h before cadmium chloride (CdCl2) treatment (40 µM), and then DNA damage was evaluated by comet assay. Furthermore, DPPH and free thiol group assays were applied to evaluate reactive oxygen species scavenger and antioxidant capacities of osthole.

In the present study, all concentrations of osthole significantly decreased CdCl2-induced DNA damage. Furthermore, the antioxidant properties of the osthole were confirmed by DPPH and free thiol assays.

Conclusion and implications:

 Overall, the findings of this project revealed that osthole could ameliorate cadmium-induced genotoxicity probably by its antioxidant activity.

Diazepam belongs to the benzodiazepine family of drugs and is mainly used for anxiety, muscle spasms, seizures, and insomnia. Long-term diazepam administration can cause genotoxicity, and oxidative stress is a likely molecular mechanism involved.

In this study, the benefits of melatonin against diazepam-induced oxidative damage and genotoxicity were investigated.

Cultured peripheral lymphocytes were allocated to five groups: control, diazepam (100 μg/ mL), melatonin (50 and 100 μM) with diazepam and cisplatin (0.05 μg/mL). After harvesting and preparing slides, the incidence of micronuclei (MN) was observed as a marker of genotoxicity. Then, in order to measure oxidative stress parameters, contents of glutathione (GSH) and lipid peroxidation (LPO) were determined.

Results documented increased MN and LPO and decrease in GSH levels in diazepam-administered lymphocytes versus those of the control group. When melatonin was given to diazepam-administered lymphocytes, they almost attenuated the increase of MN and LPO and restored the levels of GSH.

Results showed that diazepam seems to induce genotoxicity in cultured human lymphocytes and oxidative stress plays an important role in it. Furthermore, it is concluded that melatonin efficiently protects against genotoxicity through its anti-oxidative effects.

Teucrium persicum is an Iranian endemic plant used in Iranian traditional medicine. The total phenolic and total flavonoid contents, and antioxidant potential of the methanolic extract of T. persicum were determined. The MTT test was used to evaluate the inhibitory effect of the extract on the viability of A-375 cells. The clonogenic, micronucleus formation, and acridine orange/ethidium bromide staining methods were used to evaluate the survival and proliferation of A-375 cells. Apoptosis was evaluated by using DNA fragmentation assay and measuring the activity of caspase 3/7. To study the effect of the extract on the migration of A-375 cells, the in vitro wound-healing (scratch) assay was employed. The average total phenolic and flavonoid contents and antioxidant properties of the extract were 6.97±0.011 mg Ellagic acid (EGA)/g, 46.83±0.0019 mg of the ethoxyquin (1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline; EQ)/g of dried extract, and 10±0.002 μg/ml, respectively. The IC50 value of the T. persicum methanolic extract was 13 μg/ml for 48 hr. The DNA fragmentation pattern and the activity of caspase3/7 suggested that the reduction of the cell viability may be due to apoptosis induction. Microscopic observations showed nuclear condensation, a considerable increase in micronuclei formation, and inhibition of the colony formation in A-375 cells treated with 7 μg/ml to 15 μg/ml of the extract. Wound-healing assay supported the anti-migration activity of the extract. T. persicum has significant antioxidant and cytotoxic properties. Surely, more detailed molecular and biochemical studies are needed to find the mechanism(s) behind these effects.

Most people with diabetes suffer from cardiovascular problems; however, increased oxidative stress caused by diabetes can increase the risk of DNA damage and cancer. Carvedilol is a third-generation beta-blocker that can both improve heart function and prevent oxidative stress.

The present study aimed to assess carvedilol’s genoprotective effects against hyperinsulinemia-induced DNA strand break in rats.

To evaluate the extent of DNA damage caused by high insulin concentrations and the effect of carvedilol on these lesions, isolated lymphocytes of high-fat type 2 diabetic rats were evaluated using the comet method.

Our results in this study using the comet method showed that hyperinsulinemia and hyperglycemia of high-fat diet have significant genotoxic parameters in rats (tail length 84.35 ± 0.23 vs. 0.90 ± 0.02, % DNA in tail 16.09 ± 0.09 vs. 7.63 ± 0.04, and tail moment 13.58 ± 0.09 vs. 0.07 ± 0.01) compared with the control group (P < 0.001). In rats receiving carvedilol, we observed the genoprotective effect in a dose-dependent manner, which is predicted due to the antioxidant activity of carvedilol and its metabolites.

It does not have an adverse effect on the blood sugar profile of diabetics and reduction of cardiovascular complications of the disease; carvedilol can prevent genetic damage and cancer risk in hyperinsulinemia induced by the high-fat diet.

The aim of study was the biological assessment of cultured RAW264 macrophage exposed to nano amorphous calcium phosphate particles by analyzing of cytotoxicity and genotoxicity tests.

Nanoamorphus Calcium Phosphate particles were produced by sol -gel method, then particle size and hemogenicity was analyzed by XRD (X ray Diffraction). Cytotoxicity of nanoparticles was determinated with mouse RAW264 macrophage. The cells cultured in 37°c in DMEM medium 96 part s plates with concentration of 10000 cells in each part for 72 hours, then the medium removed and the second medium added to cells containing different concentrations of Nano particle (0, 200 and 400μg/ml). After 24 hours of incubation, MTT assay and Annexin V were used for assessing cell viability and apoptosis.

The apoptosis insignificantly increased in macrophages with 200 and 400 μg/ml NACP and for cytotoxicity, cell viability for control, 200μg and 400μg groups were 100,107,103 percent.

NACP has no cytotoxicity and genotoxicity, so it can be used as non -toxic and beneficial material for clinical use.

Green based nanoparticles were synthesized to investigate the cytotoxic effects on human peripheral blood mononuclear cells (hPBMCs). Nanoparticles were made by mixing using aqueous Allamanda cathartica L. latex (3%) and magnesium oxide (1mM) at 370C on shaker for 24 hours. The developed nanoparticles were characterized by Scanning Electron Microscopy, Transmission Electron Microscopy, Fourier Transmission Infra-Red, Zeta potential and X-ray diffraction. in vitro hPBMCs were tested in vitro with different concentrations of synthesized nanoparticles and found maximum concentration at that 100 µg/mL showed about 96% dead cells from trypan blue dye exclusion method. Though controlling the proliferation of cells, the nanoparticles did not exhibit any genotoxicity, indicating that the nanoparticles showed their effect on periphery of the cells, broke them that led to the death of cells. This is the first report of green route development of MgO nanoparticles using the latex of Allamanda cathartica L. and finding their efficacy on hPBMCs. Further analysis is required to confirm their use as therapeutics in leukemia.

Cisplatin is a cancer chemotherapeutic drug that has been extensively used in the treatment of a variety of cancers. However, the full usage of cisplatin is limited due to its treatment associated development of multiple side effects in the host. In the present study, the modulatory effect of rutin, a type of flavonoid, on the cisplatin mediated antitumor activity and allied genotoxicity in ascites Dalton’s lymphoma (DL)-bearing mice were investigated.

The antitumor activity was determined by calculating the percent increase in the life span of mice, cell viability and scanning electron microscopy (SEM) of DL cells. Further, the modulatory effect of rutin on the cisplatin-induced genotoxic effects in the same DLbearing mice was assessed by the analysis of micronuclei, chromosomal aberration and sperm abnormality.

The combination treatment of mice with rutin and cisplatin showed a considerable increase in the life span of the DL-bearing mice depicting better antitumor efficacy. SEM of these DL cells showed severe membrane deformities in DL cells such as fusion of cell membrane, membrane blebbing, cell shrinkage, membrane folding and loss in microvilli from the tumor cell surface which may lead to cell death. Cisplatin alone treatment caused an increase in the frequency of chromosomal aberrations, micronuclei and sperms abnormality. However, the combination treatment of DL-bearing mice with rutin and cisplatin comparatively reduced these genotoxic effects.

The overall findings suggest that rutin enhances the cisplatin-mediated antitumor activity and cytotoxicity against DL cells and at the same time diminishes the genotoxic effects induced by cisplatin in the DL-bearing mice.

Aflatoxin B1 is one of the main poisonous substances in certain kinds of fungi all over the world. The toxin is a serious health threat to humans and livestock, particularly via DNA damage, and induces multiple cancers. Probiotic agents have confirmed positive beneficial effects in DNA protection against various toxic compounds. In this regard, the present study aimed to investigate the bio-protective effects of a native Lactobacillus plantarum subsp. plantarumNIMBB003 strain isolated from Iranian one-humped camel milk against AflatoxinB1 (AFB1)-induced genotoxicity damage, based on the micronucleus test as a genotoxicity monitoring method.

In this study, a human male blood sample was treated and incubated with107, 109, and 1011CFU/mL of viable L. plantarum and IC50 dose ofAFB1alone and in combination. Afterward, assessed the rate of production of the micronucleus in bi-nucleated lymphocytes. It must be noted that a p-value of less than0.05 was considered significantly significant.

Based on the findings, the combined treatment of the L. plantarum at 1011 and109CFU/mL dose with 5.33±0.57% of the micronuclei fragments had protective effects and significantly decreased the genotoxicity of AFB1 by 76%.

According to the findings, it can be concluded that L. plantarum in 109 CFU/mL had high protective potency against AFB1 genotoxicity. Consequently, the use of local, natural, and native protected compounds with antioxidant effects, such as probiotics agents, is one of the objectives of developing a green strategy in macro-management policies for the discovery and production of new medicines and functional foods with protective/therapeutic effects against nutritional and endogenous DNA toxins