Frequency Of Sister Chromatid Exchanges Research Articles

The Effects of Aflatoxin B1 on Chromosome Aberrations and Sister Chromatid Exchanges in Human Lymphocytes

Aflatoxin B1 (AFB1) is a ubiquitous mycotoxin produced by toxicogenic Aspergillus species. AFB1 has been reported to cause serious adverse health effects, such as cancers and abnormal development and reproduction, in animals and humans. The aim of this study was to investigate the ability of aflatoxin B1 (AFB1) to induce chromosome aberrations (CA) and sister chromatid exchanges (SCE) in human lymphocytes. AFB1 exposure significantly increased the number of CA and the frequency of SCE when compared with the control group. This significant increase in CAs as well as SCE may be attributed to the fact that AFB1 can induce genotoxicity through DNA damage. Thus, the present study indicates that AFB1 was genotoxic in human lymphocytes.

Carbon Disulfide (CS2) Induced Chromosomal Alterations and Apoptosis in Circulated Blood Lymphocytes of Personnel Working in Viscose Industry

Background and objective: Carbon disulfide (CS2) is a naturally occurring chemical substance in the environment and also an important endogenous substance in the human body. This study was done to collect data on the effects and to find a possible relationship between in-vivo CS2 induced apoptosis and genotoxic effects.Material and method: Circulated blood lymphocytes (PBL) of 41 workers occupationally exposed to Carbon disulfide (CS2) in viscose industry were investigated. The participants involved three groups. The first group included 41 participants exposed to CS2 together with various confounding factors; the second group comprised of 41 participants who were inhabitant of viscose industry and were partially exposed to CS2 in long periods; and third group consisting 41 participants as control group who were not exposed to any kind of chemicals and radiation hazards. Ambient air concentrations of CS2 were measured in different workplaces. Measures of genotoxicity included the determination of the frequencies of chromosomal aberrations (CA), sister-chromatid exchange (SCE), HPRT mutations (variant frequency, VF), and measurement of UV-induced unscheduled DNA-repair synthesis (UDS). The percentages of premature centromere division (PCD) and of cells with a high frequency of SCE (HF/SCE) were also scored. Apoptosis and c l proliferation were determined by flow cytometry.Results: In both CS2 exposed groups, the apoptotic activity and the CA levels in PBLs were significantly higher than in controls. CA was mostly breaks of the chromatid type. In group II, CA was slightly lower in comparison with group I, which can be attributed to a different rate of elimination of damaged lymphocytes as a consequence of CS2 induced apoptotic activity.Conclusion: The results demonstrate that exposure to CS2 induced apoptosis and CA, indicating an excess cancer risk among participants occupationally exposed to CS2. The results also emphasized the importance of the measurement of occupationally exposed pollutants such as CS2 in order to avoid genotoxic effects in the workers.

The effect of phototherapy on sister chromatid exchange with different light density in newborn hyperbilirubinemia.

Concerns of possible genotoxic effects of hyperbilirubinemia and phototherapy were raised from experimental and observational studies in neonates. The purpose of this study was to assess the effect of hyperbilirubinemia and phototherapy with three different methods on DNA damage by investigating sister chromatid exchange frequency. Patients whose gestational ages were >37 weeks and bilirubin levels above phototherapy limits were enrolled into three groups and each group was planned to receive 25 babies. Group 1 received enhanced light-emitting diode phototherapy, group 2 had light-emitting diode phototherapy, and group 3 received conventional phototherapy. Infants with hyperbilirubinemia but did not require phototherapy comprised the control group, which was subdivided into two groups regarding bilirubin levels (<or>10mg/dL). Blood samples were collected before and after phototherapy for sister chromatid exchange frequency and samples were examined by a biologist who was blinded to the study groups. The mean pre-treatment sister chromatid exchange frequency was 1.41±0.34/cell, post-treatment 2.65±0.68/cell, and 1.61±0.61/cell for the control group (p<0.05). A statistically significant increase in sister chromatid exchange frequency after phototherapy was observed in all three intervention groups (p values: 0.01, 0.01, and 0.008, respectively). When the treatment groups were compared with each other in terms of irradiance, no significant difference was found (p=0.08). Phototherapy causes an increase in the frequency of sister chromatid exchange regardless of the irradiance. Phototherapy could have some genotoxic adverse effects on chromosomes; however, further investigations are warranted to enlighten as to whether these effects are permanent or clinically important.

Investigation of in vitro genotoxic effects of an anti-diabetic drug sitagliptin

Sitagliptin is an active ingredient of antidiabetic drug used in the treatment of type 2 diabetes mellitus (T2DM). In this study, the genotoxic effects of sitagliptin were determined in human lymphocytes by using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronucleus (MN) and comet assays. 31.25–1000 μg/mL concentrations of sitagliptin were used. Sitagliptin significantly increased the frequency of CAs and SCEs at the highest concentration at 24 h treatment and all concentrations (except 250 μg/mL for CA, except 31.25 and 62.50 μg/mL for SCE) at 48 h treatment compared with solvent control (DMSO). This compound increased the MN at only the highest concentration compared with the solvent control. Mitotic index (MI) significantly decreased at the three highest concentrations of sitagliptin at 48 h treatment. However, replication (RI) and nuclear division (NDI) indices were not affected at all the treatments. Comet assay results indicated that sitagliptin significantly increased mean comet tail intensity and tail moment at only two concentrations (62.50 and 1000 μg/mL for intensity, 125 and 1000 μg/mL for tail moment), and tail length at all concentrations (except 125 and 500 μg/mL). It was concluded that higher concentration of sitagliptin had genotoxic effects in the human lymphocytes in vitro.

Anti-mutagenic and Anti-oxidant Potencies of Cetraria Aculeata(Schreb.) Fr.,Cladonia Chlorophaea(Flörke ex Sommerf.) Spreng. andCetrelia olivetorum(Nyl.) W.L. Culb. & C.F. Culb.).

In this study, the mutagenic and anti-mutagenic effects of methanol extract of three lichen species (Cetraria aculeata, Cladonia chlorophaea and Cetrelia olivetorum) were investigated by using E. coli-WP2, Ames-Salmonella (TA1535 and TA1537) and sister chromatid exchange (SCE) test systems. The results obtained from bacterial test systems demonstrated that methanol extracts of three lichen species have strong anti-mutagenic potencies on TA1535, TA1537 strains and to a lesser extent on E. coli-WP2 strain. The anti-oxidant level of human lymphocytes cells was determined in order to clarify the mechanism underlying the anti-mutagenic effects of these lichen species. Co-treatments of 5, 10 and 20 µg/mL concentrations of these three lichen species with AFB decreased the frequencies of SCE and the level of MDA and increased the amount of SOD, GSH and GPx which decreased by aflatoxin. The findings of this work have clearly demonstrated that Cetraria aculeata, Cladonia chlorophaea and Cetrelia olivetorum have significant anti-mutagenic effects which are thought to be partly due to the anti-oxidant activities and the interaction capability of lichen extracts with mutagen agents (Sodium azide, acridin, N-methyl-N'-nitro-N-nitrosoguanidine and aflatoxin B1).

Hypersensitivity of mouse embryonic fibroblast cells defective for DNA polymerases η, ι and κ to various genotoxic compounds: Its potential for application in chemical genotoxic screening

Genotoxic agents cause modifications of genomic DNA, such as alkylation, oxidation, bulky adduct formation, and strand breaks, which potentially induce mutations and changes to the structure or number of genes. Majority of point mutations are generated during error-prone bypass of modified nucleotides (translesion DNA synthesis, TLS); however, when TLS fails, replication forks stalled at lesions eventually result in more lethal effects, formation of double-stranded breaks (DSBs). Here we compared sensitivities to various compounds among mouse embryonic fibroblasts derived from wild-type and knock-out mice lacking one of the three Y-family TLS DNA polymerases (Polη, Polι, and Polκ) or all of them (TKO). The compounds tested in this study include genotoxins such as methyl methanesulfonate (MMS) and nongenotoxins such as ammonium chloride. We found that TKO cells exhibited the highest sensitivities to most of the tested genotoxins, but not to the non-genotoxins. In order to quantitatively evaluate the hypersensitivity of TKO cells to different chemicals, we calculated ratios of half-maximal inhibitory concentration for WT and TKO cells. The ratios for 9 out of 10 genotoxins ranged from 2.29 to 5.73, while those for 5 nongenotoxins ranged from 0.81 to 1.63. Additionally, the two markers for DNA damage, ubiquitylated proliferating cell nuclear antigen and γ-H2AX after MMS treatment, were accumulated in TKO cells more greatly than in WT cells. Furthermore, following MMS treatment, TKO cells exhibited increased frequency of sister chromatid exchange compared with WT cells. These results indicated that the hypersensitivity of TKO cells to genotoxins resulted from replication fork stalling and subsequent DNA double-strand breaks, thus demonstrating that TKO cells should be useful for evaluating chemical genotoxicity.

Vitamin E protects human lymphocytes from genotoxicity induced by oxaliplatin

Oxaliplatin is a platinum-based anticancer drug that has been shown to be genotoxic to the normal cells. Vitamin E is a potent antioxidant that may protect and enhance the repair of the damaged DNA. In this study, we aimed to evaluate the genotoxic effect of oxaliplatin on DNA by measuring the frequency of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in cultured human lymphocytes. We also attempted to explore the potential protective effect of vitamin E on chromosomal damage induced by oxaliplatin. Results showed that oxaliplatin significantly increased the frequency of CAs (p < 0.001) and SCEs (p < 0.001) as compared to control. This chromosomal damage, caused by oxaliplatin, was significantly decreased by pretreatment of cells with vitamin E. Moreover, the results showed that oxaliplatin caused a significant reduction in the cell kinetic parameters, the mitotic index (MI) and the proliferative index (PI). However, vitamin E did not affect this reduction in the MI and PI. Therefore, we conclude that oxaliplatin is genotoxic, and vitamin E can prevent the chromosomal damage induced by oxaliplatin but it has no effect on oxaliplatin-induced cytotoxicity.

Protective effect of Teucrium polium on carbon tetrachloride induced genotoxicity and oxidative stress in rats

This study aimed to investigate the protective effects of Teucrium polium (TP) on carbon tetrachloride (CCl4) induced spleen, erythrocyte’s oxidative stress, and genotoxicity in rats. TP was found to contain large amounts of polyphenols (150 mg GAE/G of dry plant) and flavonoids (60 mg QE/g of quercetin dry plant). The CCl4 (0.5 ml/kg) treated rats exhibited significant reductions in serum vitamin A (VA), vitamin E (VE) and total antioxidant status (TAS). Thiobarbituric acid reactive substances (TBARS) and conjugated dienes (CD) were significantly high in the CCl4 group compared to controls. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were significantly decreased in CCl4 rats. Cytogenetic trials revealed remarkable increases in the frequency of chromosomal aberrations (CAs) and sister chromatid exchange (SCE) following CCl4 administration. Pretreatment with TP prevented damages caused by CCl4. Spleen characterised by necrosis was detected in CCl4 as compared to controls. Pretreatment with TP considerably decreased the perturbation.

In vitro Cytotoxic and Genotoxic Evaluation of Morinda tinctoria Roxb. Leaf Extracts

The in vitro cytotoxic and genotoxic evaluation of hexane, chloroform, ethyl acetate, and methanol extracts of Morinda tinctoria leaves was carried out by MTT assay and chromosomal aberration (CA), sister chromatid exchange (SCE), cell proliferation kinetics (CPK), and mitotic index (MI) tests. Five cancer cell lines [SW480 (colon adenocarcinoma); MCF-7 (breast cancer); K562 (chronic myeloid leukemia); NCIH-23 (lung cancer); SKMEL-28 (skin melanoma)] were chosen for the MTT assay. The genotoxic evaluation was carried out on human lymphocyte cell cultures at various concentrations (5, 10, 15, 20 and 25 mg/mL). The results obtained showed (i) concentration-dependent percentage inhibition with the IC50 values of different solvent extracts for cell lines studied ranging from 3.99 to 20.84 mg/mL, (ii) decrease in MI and very slight modification in the CPK values, and (iii) statistical increase in the percentage of cells with CA and the frequency of SCE for cultures exposed to various crude extracts. This is the first report on cytotoxic and genotoxic effects of M. tinctoria leaves extracts. The results suggest that the plant extracts exhibit cytotoxic and possible genotoxic effects with increasing concentration.

Evaluation of baseline frequency of sister chromatid exchanges in an Italian population according to age, sex, smoking habits, and gene polymorphisms.

Increased SCEs frequencies in human lymphocytes are an indicator of spontaneous chromosome instability and could be influenced by different exogenous and endogenous factors. In this study, we evaluated the influence of age, sex, smoking habits, and genetic polymorphisms on the background levels of SCEs in peripheral blood lymphocytes. Two hundred-thirty healthy Italian subjects were recruited. Data about age, sex and smoking habits were recorded. Subjects were also genotyped for GSTT1, GSTM1, GSTP1 A/G, CYP1A1 Ile/Val, CYP2C19 G/A, ERCC2/XPD Lys751Gln, XRCC1 Arg194ATrp, XRCC1 Arg399Gln, and XRCC1Arg208His gene polymorphisms. The frequency of SCEs/cell was 5.15±1.87, with females showing a significantly higher SCEs value with respect to males (5.36±2.10 and 4.82±1.39, respectively). Smokers showed significantly increased levels of SCEs with respect to nonsmokers (5.93±1.75 and 4.70±1.79, respectively) whereas no differences were observed between heavy and light smokers. Age correlated with the RI value (P=.01) but not with the SCEs frequency (P=07), although the 31-40 age group showed a significantly lower SCEs frequency with respect to the other age groups. A significant association was also found between GSTP2C19-AA, GSTT1-null, GSTM1-null, ERCC2/XPD Gln751Gln, and XRCC1 His208His genotypes, and higher frequencies of SCEs. We describe the association between some phase I, phase II, and DNA-repair gene polymorphisms with increased SCEs frequencies, reinforcing the importance of genetic analysis in biomonitoring studies. Sex and age were found to be important endogenous factors that affect the level of genomic damage and the replicative capacity of cells, respectively.

Mutagenic and genotoxic effects of Anilofos with micronucleus, chromosome aberrations, sister chromatid exchanges and Ames test.

We aimed to evaluate the mutagenic effect of Anilofos, organophosphate pesticide, by using Ames/Salmonella/microsome test. Its cytotoxic and genotoxic effects were also determined by chromosome aberration (CA), sister chromatid exchange (SCE) and micronucleus (MN) test in human peripheral blood lymphocytes. In the Ames test, five different concentrations of Anilofos were examined on TA97, TA98, TA100 and TA102 strains in the absence and presence of S9 fraction. According to the results all concentrations of this pesticide have not shown any mutagenic activity on TA97, TA100 and TA102 strains in the absence and presence of S9 fraction. But, 10, 100 and 1000µg/plate concentrations of Anilofos were determined to be mutagenic on TA98 strain without S9 fraction. Lymphocytes were treated with various concentrations (25, 50, 100 and 200µg/ml) of Anilofos for 24 and 48h. The results of the assays showed that Anilofos did not induce SCE frequency, replication index and MN formation at all concentrations for both treatment periods. Anilofos significantly increased CA frequency at 100 and 200µg/ml concentrations at 24h treatment periods and at 50, 100 and 200µg/ml concentrations in 48h treatment periods. Additionally, it was determined that this pesticide decreased mitotic index and nuclear division index significantly. It was concluded that Anilofos has genotoxic and cytotoxic effects in human peripheral lymphocytes.

Early detection of lung cancer potential among Egyptian wood workers.

Wood dust is known to be a human carcinogen, with a considerable risk of lung cancer. The increased cancer risk is likely induced through its genotoxic effects resulting from oxidative DNA damage. This study aimed at assessing the genotoxicity of wood dust and demonstrating the role of sputum PCR as a screening tool for early prediction of lung cancer among wood workers. The study was carried out in the carpentry section of a modernized factory involved with the manufacture of wooden furniture in Greater Cairo, Egypt. Environmental assessment of respirable wood dust concentrations was done. Frequency of chromosomal aberrations (CA%) and sister chromatid exchanges (SCE%) in peripheral blood lymphocytes (PBL) was assessed and comet assays were performed in samples from among the study population (n=86). Levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes were measured. The polymerase chain reaction (PCR) was used to study hypermethylation of p16 and ̸or O6-methylguanine-DNA methyltransferase (MGMT) gene promoters in sputum DNA. The concentrations of respirable wood dust exceeded the Egyptian and international permissible limits with highest levels generated by sawing operations. Laboratory investigations revealed statistically significantly higher frequencies of CA and SCE as well as increased comet tail length associated with significant decrement in the levels of SOD and GPx among exposed group. A statistically significant elevation in the extent of hypermethylation was detected for the p16 and MGMT gene promoters in the sputum DNA of studied wood workers. The study results support the conclusion that prolonged unprotected occupational exposure to wood dust is associated with possible genotoxicity and oxidative stress that might raise the risk for carcinogenesis including lung cancer.

Abstract B37: PARP inhibitor olaparib induces genomic instability in normal mammalian cells

Abstract Poly(ADP-ribose) polymerases (PARPs) are the first proteins involved in cellular DNA damage response pathways to be targeted by specific inhibitors for clinical benefit. Tumors with defects in homologous recombination (HR) are hypersensitive to PARP inhibitors (PARPi), and early phase clinical trials have been promising in patients with advanced BRCA1 and BRCA2-associated breast, ovary and prostate cancer. Unlike HR-defective cells, HR-proficient cells manifest low cytotoxicity when exposed to PARPi. Nonetheless, they mount a DNA damage response and show a genomic instability phenotype as demonstrated by an increased frequency of sister chromatid exchange. To study molecular mechanisms underlying PARPi-generated genomic instability, we took advantage of olaparib an agent in clinical use. Our results in mouse embryonic stem cells show that olaparib increases HR leading to copy number alterations and induces a mutator phenotype. Further, using a genome wide approach we finally demonstrate that PARPi treatment increases DNA double-strand breaks genome-wide which can lead to translocations and other genome aberrations. Our findings have important implications for therapies with regard to sustained genotoxicity to normal cells. Genomic instability arising from PARPi warrants consideration in prevention strategies or for non-oncologic indications. Citation Format: Fabio Vanoli, Shuhei Ito, Richard L. Frock, Frederick W. Alt, Mary Ellen Moynahan, Maria Jasin. PARP inhibitor olaparib induces genomic instability in normal mammalian cells [abstract]. In: Proceedings of the AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; 2016 Nov 2-5; Montreal, QC, Canada. Philadelphia (PA): AACR; Mol Cancer Res 2017;15(4_Suppl):Abstract nr B37.

Retrospective Biological Dosimetry at Low and High Doses of Radiation and Radioiodine Impact on Individual Susceptibility to Ionizing Radiation.

Iodine-131 (I-131) is often used in thyroid diagnostics and therapy. External and internal exposure to radioiodine can lead to molecular and cellular damage in peripheral blood lymphocytes. The aim of this study was to explore the influence of low and high doses of I-131 on susceptibility to ionizing radiation. Study groups consisted of 30 individuals free of thyroid diseases, 41 patients exposed diagnostically to low doses of I-131, and 37 hyperthyroidism patients exposed therapeutically to high doses. The standardized DNA repair competence assay was used to test the efficacy of the fast DNA repair process in G0 cells. Cytogenetic preparations were made in fresh blood samples before and after challenging cells in vitro with X-ray dose. The frequency of sister chromatid exchanges (SCE) and percentage of cells with significantly elevated numbers of SCE were used as cytogenetic biomarkers associated to homologous recombination and compared to reported earlier cytogenetic biomarkers of cancer risk. Strong individual variation in the biomarkers is observed in all investigated groups before and after challenging. Nevertheless, the efficiency of post challenging fast repair is significantly high in the patients exposed to diagnostic I-131 doses than in unexposed control group and linked to decreased cytogenetic damage. However, 5 weeks after administration of therapeutic doses, significant increases of unrepaired post challenging DNA and cytogenetic damages were observed indicating a health risk. Results also suggest that the appearance of cancers in immediate families might influence DNA repair differently in patients exposed to low than to high doses.

Antioxidant and Genotoxic Properties of Hispidin Isolated from the Velvet-Top Mushroom, Phaeolus schweinitzii (Agaricomycetes).

Antioxidant and genotoxic properties of hispidin isolated from the Phaeolus schweinitzii mushroom were evaluated with various assays. Hispidin demonstrated strong free radical scavenging, oxygen radical absorbance capacity, and ferric-reducing antioxidant power; in all applied assays, hispidin exhibited antioxidant capacity similar to or higher than that of the reference antioxidant Trolox. Genotoxic activity of hispidin was assessed using different end points: chromosome aberrations, micronuclei, sister chromatid exchanges, and primary DNA damage (detected by the comet assay) in human lymphocytes in vitro, and gene mutations in the Salmonella/microsome test. Hispidin did not increase the frequency of chromosome aberrations, micronuclei, or primary DNA damage in human lymphocytes in vitro and did not produce reverse mutation in bacterial cells. However, we identified in human lymphocytes a statistically significant dose-dependent increase in sister chromatid exchange frequency and a decrease in replication index and nuclear division index values.

Evaluation of genotoxic effects of 3-methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione on human peripheral lymphocytes

Context: Tranexamic acid is commonly used for curing abnormal bleeding in a variety of diseases. In a previous study, 12 different tetrahydro-2H-1,3,5-thiadiazine derivatives were synthesized from the amine group of tranexamic acid. Their antifibrinolytic and antimicrobial activities were compared with tranexamic acid. 3-Methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione (3-MTTT) was the most remarkable one, which may be used as a drug. Objectives: In vitro genotoxicity of 3-MTTT was investigated using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronucleus (MN) and comet assays. Materials and methods: Various concentrations 0.78, 1.56, 3.13, 6.25, 12.50 and 25.00 μg/mL of 3-MTTT were applied to lymphocytes obtained from two donors for periods of 24 and 48 h. A negative (distilled water), a solvent (2:1 PBS:10% NaOH for cultured lymphocyte, and PBS for isolated lymphocytes) and a positive control (MMC for cultured lymphocytes and H2O2 for isolated lymphocytes) were also maintained. Results: While this compound did not increase the frequency of abnormal cells and CA/cell ratio compared to negative control (except 48 h, 25 μg/mL), it significantly increased the frequency of SCEs at the four highest concentrations at both treatment periods (except 6.25 μg/mL, 48 h). It significantly decreased the MI in all the concentrations at 24 h (except 0.78 μg/mL) and in the highest three concentrations at 48 h. This compound did not significantly increase the frequency of MN and DNA damage compared to negative control. This compound did not affect the replication and nuclear division index. Discussion and conclusion: Our results demonstrated that this compound does not represent a significant risk at the genetic level in in vitro human lymphocytes.

Protective effect of thymoquinone against cyclophosphamide-induced genotoxic damage in human lymphocytes.

Protective effect of thymoquinone (TQ) against the cytotoxic and genotoxic effects of cyclophosphamide (CP) was assessed in human peripheral blood lymphocyte culture. Mitotic indices were determined as endpoints of cytotoxicity, while sister chromatid exchanges (SCE) served as endpoints of genotoxicity. Firstly, the genotoxic effect of 0.16 µg/ml of CP was tested and CP was detected as genotoxic. In the second set, CP group was treated with 20 µM and 40 µM TQ. TQ reduced the SCE frequencies, suggesting its protective action on human lymphocytes in vitro against the CP induced genotoxic damage. Our results suggest that TQ produces a protective mechanism against CP-induced genetic damage, and suggest a role of DNA strand breaks in the genotoxicity (Tab. 1, Fig. 1, Ref. 19).

In vitro Effects of Epigallocatechin Gallate on Sister Chromatid Exchange in the Lymphocytes Exposed to Glyphosate

Purpose: Green tea is known as a potent anti-oxidant, anti-carcinogen, and genetic protector. Glyphosate (N-phosphonomethyl glycine) is a widely used non-selective herbicide that causes DNA damage. The present study was conducted to investigate the protective effects of green tea in human blood lymphocytes exposed to glyphosate using the Sister Chromatid Exchange (SCE) frequency method. Methods: Peripheral blood was obtained from 10 volunteers and cultured through four different conditions. Four groups were divided into control, glyphosate only (300 ng/mL), glyphosate and low ($20{mu}m$) concentrations of epigallocatechin gallate (EGCG) and glyphosate and high ($100{mu}m$) concentrations of EGCG. Results: The glyphosate exposed groups had a higher mean SCE frequency ($10.33{pm}2.50$) than the control group ($6.38{pm}2.28$, p&lt;0.001). The low concentrations of EGCG groups had a lower mean SCE frequency ($9.91{pm}1.93$) than the glyphosate-only group, although this difference was not significant (p=0.219). However, the high concentration group ($9.49{pm}1.85$) had a significantly lower SCE frequency than the glyphosate-only group (p=0.001). Conclusion: EGCG has a gene protective effect in human lymphocytes exposed to the genotoxicity of glyphosate in the case of high concentrations.

Genoprotective Effect of Melatonin Against to the Genotoxicity of Glyphosate on Human Blood Lymphocytes

Purpose: Glyphosate is a widely used non-selective herbicide. Previous studies have shown that glyphosate has genotoxicity, and that even low-doses of glyphosate can cause DNA damage. Melatonin is a hormone produced and secreted by the pineal gland that is known to be a potent anti-carcinogen, anti-oxidant, and genetic protector. This study was conducted to investigate the genoprotective effect of melatonin against glyphosate in human blood lymphocytes. Methods: Human peripheral blood was obtained from 15 young, healthy volunteers and cultured under four different toxicologic conditions. The four groups consisted of a control group, glyphosate only group (300 ng/mL), glyphosate with low level of melatonin group ($50{mu}M$), and glyphosate with high level of melatonin group ($200{mu}M$). The mean Sister Chromatid Exchange (SCE) frequency of each group was then analyzed. Results: Glyphosate exposed groups had a higher mean SCE frequency ($10.33{pm}2.50$) than the control group ($6.78{pm}2.31$, p&lt;0.001). Interestingly, the group that received a low-level of melatonin had a lower mean SCE frequency ($8.67{pm}2.58$) than the glyphosate-only group, while the group that received a high level of melatonin had a much lower mean SCE frequency ($8.06{pm}2.50$) than the glyphosate-only group. There was statistical significance. Conclusion: Melatonin exerted a potent gene protective effect against the genotoxicity of glyphosate on human blood lymphocytes in a dose-dependent fashion.

Genotoxicity of Casiopeina III-Ea in mouse bone marrow cells

Casiopeina III-Ea® (Cas III-Ea®) is a chelated copper complex with antineoplastic activity that is capable of reducing tumor size and inducing antiproliferative and apoptotic effects. However, little is known about its in vivo genotoxic effects. Therefore, this study evaluated two cytogenetic and two proliferative parameters 24 h after the administration of Casiopeina III-Ea® to male CD-1 mice. Three doses of Cas III-Ea® were administered by intraperitoneal injections of 1.69, 3.39 and 6.76 mg/kg (corresponding to 1/8, 1/4 and 1/2 of LD50, respectively). A reduction in the mitotic index (MI) and an increased numbers of cells with structural chromosomal aberrations (SCA) were detected. Additionally, a low but significant increase in the frequency of sister chromatid exchange (SCE) was observed at the highest dose. Changes in the DNA replication index (RI) were not observed. These results indicate that Casiopeina III-Ea® shows cytotoxic and clastogenic activity in bone marrow cells from treated mice.