Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 cells.

Curcumin is extensively used as a spice and pigment and has anticarcinogenic effects that could be linked to its antioxidant properties. However, some studies suggest that this natural compound possesses both pro- and antioxidative effects. In this study, we found that curcumin induced DNA damage to both the mitochondrial and nuclear genomes in human hepatoma G2 cells. Using quantitative polymerase chain reaction and immunocytochemistry staining of 8-hydroxydeoxyguanosine, we demonstrated that curcumin induced dose-dependent damage in both the mitochondrial and nuclear genomes and that the mitochondrial damage was more extensive. Nuclear DNA fragments were also evident in comet assays. The mechanism underlies the elevated level of reactive oxygen species and lipid peroxidation generated by curcumin. The lack of DNA damage at low doses suggested that low levels of curcumin does not induce DNA damage and may play an antioxidant role in carcinogenesis. But at high doses, we found that curcumin imposed oxidative stress and damaged DNA. These data reinforce the hypothesis that curcumin plays a conflicting dual role in carcinogenesis. Also, the extensive mitochondrial DNA damage might be an initial event triggering curcumin-induced cell death.     

阿莫西林对人HepG2细胞DNA有短暂损伤作用

目的 为了探讨阿莫西林对人HepG2细胞DNA是否有损伤作用.方法 培养的人HepG2细胞经不同浓度(2、10、50和250μmol/L)阿莫西林处理1h或经50μmol/L阿莫西林处理不同时间(20、40、60、120和180min)后,运用单细胞凝胶电泳(SCGE)技术结合彗星图像软件(CASP)分析细胞尾部DNA百分率(tail DNA%)变化情况.结果 不同浓度阿莫西林处理后结果显示,HepG2细胞尾部DNA百分率明显升高,至50μmol/L阿莫西林时达到最高值,各浓度处理组与不处理对照组相比差异皆有显著性(P<0.01);而同一浓度(50μmol/L)阿莫西林处理不同时间后结果显示,HepG2细胞尾部DNA百分率逐渐升高,至1h处理时间点时达到最高值,其后随着处理时间延长HepG2细胞尾部DNA百分率逐渐降低.结论 阿莫西林对人HepG2细胞DNA有短暂损伤作用,阿莫西林诱发的HepG2细胞DNA损伤可能随时间延长逐渐被HepG2细胞本身修复除去.     

福莫司汀对培养的HL60细胞DNA的损伤

福莫司汀对培养的ＨＬ６０细胞ＤＮＡ的损伤寿江１，冯杏婉（北京药理毒理研究所，北京１００８５０，中国）１ＮｏｗｉｎＤｅｐａｒｔｍｅｎｔｏｆＴｏｘｉｃｏｌｏｇｙ，ＩｎｓｔｉｔｕｔｅｏｆＲａｄｉａｔｉｏｎＭｅｄｉｃｉｎｅ，Ｂｅｉｊｉｎｇ１００８５０，Ｃｈｉ...     

WRN基因在氢醌致U937细胞DNA损伤中的作用

目的 WRN基因在氢醌(HQ)致U937细胞DNA损伤中的作用.方法 常规培养白血病细胞U937至生长对数期,低剂量HQ组、中剂量HQ组、高剂量HQ组分别以10、20、40μmol/L HQ染毒24 h及48 h,以等体积的完全培养基培养的细胞组为完全空白对照组.采用单细胞凝胶电泳(SCGE)检测细胞DNA损伤;采用免疫印迹法检测WRN蛋白的相对表达量.结果 (1)HQ可导致细胞DNA损伤,且损伤效用随染毒浓度增加而增大,48 h比24 h的DNA损伤程度增加,呈时间—剂量依赖性(P＜0.05);(2)免疫印迹结果显示,HQ染毒24 h,WRN蛋白相对表达量在各组差异无统计学意义(P＞0.05);HQ染毒48 h高剂量组分别与空白组、低剂量、中剂量中比较,WRN蛋白相对表达量呈降低的趋势(P＜0.05).结论 HQ诱导WRN蛋白表达下调影响U937细胞DNA损伤修复.     

A comparative study of chemically induced DNA damage in isolated nasal mucosa cells of humans and rats assessed by the alkaline comet assay

Single-cell microgel electrophoresis (comet) assay was used to study genotoxic effects in human nasal mucosa cells and rat nasal and ethmoidal mucosa cells in vitro. Human cells were obtained from tissue samples of 10 patients (3 females/7 males), who underwent surgery (conchotomy) for treatment of nasal airway obstruction. Rat nasal mucosa cells were derived from male Sprague-Dawley rats. Cells were exposed for 1 h to either N-nitrosodiethanolamine (NDELA), epichlorohydrin (EPI), 1,2-epoxybutane (EPB), ethylene dibromide (EDB), or 1,2-dibromo-3-chloropropane (DBCP). Dimethyl sulfoxide (DMSO) was used as negative control. Alkaline comet assay was performed according to a standard protocol and DNA damage was quantified as Olive tail moment using image analysis system. All test substances induced an increase in DNA damage in human and rat cells. The absolute amount of DNA damage in rat nasal mucosa cells was usually higher than in ethmoidal mucosa cells. Human nasal mucosa cells were found to be less sensitive than rat mucosa cells to the genotoxic activities of DBCP (lowest effective concentration in human cells [LEC(human)]: 1.5, in rat cells [LEC(rat)]: 0.01 mM) and NDELA (LEC(human): 25, LEC(rat): 12.5 mM), whereas EPB-treated cells were almost equal (LEC(human) and LEC(rat) 0.78 mM). NDELA induced a marked concomitant cytotoxicity. For EPI (LEC(human) and LEC(rat): 0.097 mM) and EDB (LEC(human): 0.195, LEC(rat): 0.048 mM), pronounced interindividual differences were observed in human samples.     

DNA damage and alterations in expression of DNA damage responsive genes induced by TiO2 nanoparticles in human hepatoma HepG2 cells

Abstract

We investigated the genotoxic responses to two types of TiO₂ nanoparticles (<25 nm anatase: TiO₂-An, and <100 nm rutile: TiO₂-Ru) in human hepatoma HepG2 cells. Under the applied exposure conditions the particles were agglomerated or aggregated with the size of agglomerates and aggregates in the micrometer range, and were not cytotoxic. TiO₂-An, but not TiO₂-Ru, caused a persistent increase in DNA strand breaks (comet assay) and oxidized purines (Fpg-comet). TiO₂-An was a stronger inducer of intracellular reactive oxygen species (ROS) than TiO₂-Ru. Both types of TiO₂ nanoparticles transiently upregulated mRNA expression of p53 and its downstream regulated DNA damage responsive genes (mdm2, gadd45α, p21), providing additional evidence that TiO₂ nanoparticles are genotoxic. The observed differences in responses of HepG2 cells to exposure to anatase and rutile TiO₂ nanoparticles support the evidence that the toxic potential of TiO₂ nanoparticles varies not only with particle size but also with crystalline structure.     

Protective effect of N-acetylcysteine against DNA damage and S-phase arrest induced by ochratoxin A in human embryonic kidney cells (HEK-293)

N-acetylcysteine (NAC) has recently gained particular interest as a beneficial antioxidant. This study investigated the protective effects of NAC against ochratoxin A (OTA)-induced DNA damage and S-phase arrest in human embryonic kidney cells (HEK-293). OTA exposure results in nephrotoxicity, hepatotoxicity as well as immunotoxicity; and, in the present study, the toxicity of OTA toward HEK-293 cells was explored by analyzing the involvement of the oxidative pathway. It was found that OTA treatment led to oxidative damage; meanwhile, OTA treatment induced significant DNA damage and S-phase arrest by down-regulating cyclin A2, cyclin E1, and CDK2 expression. However, NAC pretreatment alleviated OTA-induced ROS overproduction, the loss of mitochondrial membrane potential (ΔΨ_m), and the decrease in superoxide dismutase (SOD) activity. NAC pretreatment was also discovered to attenuate OTA-induced DNA damage using the comet assay and by determining the expression of γ-H2AX. In addition, NAC pretreatment partly ameliorated OTA-induced S-phase arrest by preventing the down-regulation of cyclin A2, cyclin E1 and CDK2 expression in HEK-293 cells. All of these results demonstrated that oxidative damage was involved in OTA-induced DNA damage and cell cycle arrest in HEK-293 cells. Therefore, NAC has the potential to reverse the DNA damage and S-phase arrest induced by OTA.     

全合成Jaspine B诱导人乳腺癌MDA-MB-231细胞凋亡及DNA损伤

目的研究全合成Jaspine B对人乳腺癌MDA-MB-231细胞的增殖抑制及凋亡诱导作用,并探讨其对细胞DNA的损伤。方法酸性磷酸酶法(APA)检测细胞增殖,荧光显微镜、透射电镜(TEM)观察细胞形态结构,DNA琼脂糖凝胶电泳检测DNA片段化,流式细胞技术检测凋亡率及线粒体膜电位(ΔΨm),Western blot检测凋亡相关蛋白表达,单细胞凝胶电泳(SCGE)检测DNA损伤。结果Jaspine B抑制细胞增殖,24、48、72h IC50分别为2.61、1.07、0.77μmol·L-1,其作用在一定范围内呈浓度和时间依赖性;细胞发生凋亡形态改变,生化特征上出现DNA梯状改变;1.50μmol·L-1及3.00μmol·L-1Jaspine B作用24h,早期凋亡细胞率分别为7.60%及15.48%,相应浓度作用48h,早期凋亡细胞率分别增至21.48%及23.60%;Jaspine B可引起ΔΨm明显下降、Cyt C水平增加,促使Caspase-3酶原剪切活化;Jaspine B作用24h,细胞出现明显DNA损伤。结论全合成Jaspine B对人乳腺癌MDA-MB-231细胞抑制增殖、诱导凋亡并诱发DNA损伤,凋亡经由依赖胱天蛋白酶的内在途径发生。     

Furazolidone induced oxidative DNA damage via up-regulating ROS that caused cell cycle arrest in human hepatoma G2 cells

Furazolidone (FZD) is an antimicrobial agent that has been shown to have mutagenic, genotoxic and potentially carcinogenic properties when tested in a variety of systems in vitro and in vivo. In this study, we investigated FZD's DNA damaging effect in human hepatoma cells aiming at further defining the molecular mechanism of FZD's cytotoxicity. Addition of FZD resulted in cell growth suppression and cell cycle arrest in S phase accompanied by remarkable DNA strand breaks with increased levels of intracellular reactive oxygen species (ROS) and 8-hydroxydeoxyguanosine. Activities of antioxidases were down-regulated following FZD treatment and antioxidant agent catalase and superoxide dismutase ameliorated FZD's DNA damaging effects. Moreover, FZD caused much more extensive damage to mitochondrial DNA (mtDNA) than to nuclear DNA for which the decrease in mtDNA content correlated with FZD usage in a dose-dependent manner. However, there was no evidence of FZD induced mtDNA mutation in the mitochondrial DNA displacement loop. These results demonstrate that FZD up-regulates the production of intracellular ROS to cause oxidative DNA damage with mtDNA being the most vulnerable targets. Oxidative stress and the injury of mtDNA could be early indicators of FZD-induced cytotoxicity, with the resulting abnormal progression of the cell cycle.     

Impact of boric acid exposure at different concentrations on testicular DNA and male rats fertility

Abstract

The aim of this study was to investigate the consequences of exposure to three levels of boric acid (BA) on male rats reproduction, fertility and progeny outcome, with emphasis on testicular DNA level and quality. Adult male rats (12 weeks old) were treated orally with 125, 250 and 500?mg/kg?bwt/d of BA for 60?d. The results indicated that BA administration at 125?mg/kg?bwt had no adverse effects on fertility, sperm characteristics or prenatal development of the impregnated females. However, at dose 250?mg, BA treatment significantly increased serum nitric oxide, testosterone, estradiol levels and testicular boron and calcium levels and also significantly reduced serum arginase activity, sperm quality and testicular DNA content with minor DNA fragmentation. The impact of BA exposure at dose 250?mg on male rats fertility was translated into increases in pre-implantation loss with a resulting decrease in the number of live fetuses/litter. In addition to the significant alteration of biochemical measurements, observed at dose 250?mg, administration of BA at 500?mg caused testicular atrophy, severe damage of spermatogenesis, spermiation failure and significant reduction of Mg and Zn testicular levels. None of the male rats, treated with 500?mg/kg?bwt, could impregnate untreated females, suggesting the occurrence of definitive loss of fertility. In conclusion, BA impaired fertility, in a dose-dependant manner, by targeting the highly proliferative cells, the germ cells, through decreasing DNA synthetic rate rather than the induction of DNA damage.     

Genotoxicity of nanomaterials: DNA damage and micronuclei induced by carbon nanotubes and graphite nanofibres in human bronchial epithelial cells in vitro

Despite the increasing industrial use of different nanomaterials, data on their genotoxicity are scant. In the present study, we examined the potential genotoxic effects of carbon nanotubes (CNTs; >50% single-walled, ∼40% other CNTs; 1.1 nm × 0.5–100 μm; Sigma–Aldrich) and graphite nanofibres (GNFs; 95%; outer diameter 80–200 nm, inner diameter 30–50 nm, length 5–20 μm; Sigma–Aldrich) in vitro. Genotoxicity was assessed by the single cell gel electrophoresis (comet) assay and the micronucleus assay (cytokinesis-block method) in human bronchial epithelial BEAS 2B cells cultured for 24 h, 48 h, or 72 h with various doses (1–100 μg/cm², corresponding to 3.8–380 μg/ml) of the carbon nanomaterials. In the comet assay, CNTs induced a dose-dependent increase in DNA damage at all treatment times, with a statistically significant effect starting at the lowest dose tested. GNFs increased DNA damage at all doses in the 24-h treatment, at two doses (40 and 100 μg/cm²) in the 48-h treatment (dose-dependent effect) and at four doses (lowest 10 μg/cm²) in the 72-h treatment. In the micronucleus assay, no increase in micronucleated cells was observed with either of the nanomaterials after the 24-h treatment or with CNTs after the 72-h treatment. The 48-h treatment caused a significant increase in micronucleated cells at three doses (lowest 10 μg/cm²) of CNTs and at two doses (5 and 10 μg/cm²) of GNFs. The 72-h treatment with GNFs increased micronucleated cells at four doses (lowest 10 μg/cm²). No dose-dependent effects were seen in the micronucleus assay. The presence of carbon nanomaterial on the microscopic slides disturbed the micronucleus analysis and made it impossible at levels higher than 20 μg/cm² of GNFs in the 24-h and 48-h treatments. In conclusion, our results suggest that both CNTs and GNFs are genotoxic in human bronchial epithelial BEAS 2B cells in vitro. This activity may be due to the fibrous nature of these carbon nanomaterials with a possible contribution by catalyst metals present in the materials—Co and Mo in CNTs (<5 wt.%) and Fe (<3 wt.%) in GNFs.     

DNA fragmentation and DNA repair synthesis induced in rat and human thyroid cells by four rat thyroid carcinogens

Four chemicals that are known to induce in rats thyroid follicular-cell adenomas and carcinomas were assayed for their ability to induce DNA damage and DNA repair synthesis in primary cultures of human thyroid cells. Significant dose-dependent increases in the frequency of DNA single-strand breaks and alkali-labile sites, as measures by the Comet assay, were obtained after a 20-h exposure to the following subtoxic concentrations of the four test compounds: 2,4-diaminoanisole (DAA) from 0.10 to 1.0 mM, 4,4'-methylene-bis(N,N-dimethyl)benzenamine (MDB) from 0.32 to 1.8 mM, propylthiouracil (PTU) from 1.8 to 5.6 mM, and 4,4'-thiodianiline (THA) from 0.032 to 0.18 mM. Under the same experimental conditions, DNA repair synthesis, as evaluated by quantitative autoradiography, was present in thyreocytes exposed to DAA but absent after treatment with MDB, PTU, and THA. Consistent with their thyroid-specific carcinogenic activity, all the four chemicals, administered p.o. in rats in a single dose corresponding to 1/2 LD50, induced a statistically significant degree of DNA fragmentation in the thyroid, whereas any substantial evidence of DNA lesions was absent in liver, kidney, and lung, which, with the exception of liver tumors caused by THA, are not targets of the carcinogenic activity of the four test compounds. These findings indicate that the DNA damage observed in thyroid cells was consistent with the carcinogenicity of the four test compounds, and suggest that DAA, MDB, PTU, and THA might be carcinogenic to thyroid in humans.     

Cytotoxicity and oxidative DNA damage by nanoparticles in human intestinal Caco-2 cells

Abstract

The use of engineered nanoparticles in the food sector is anticipated to increase dramatically, whereas their potential hazards for the gastrointestinal tract are still largely unknown. We investigated the cytotoxic and DNA-damaging effects of several types of nanoparticles and fine particles relevant as food additives (TiO₂ and SiO₂) or for food packaging (ZnO and MgO) as well as carbon black on human intestinal Caco-2 cells. All particles, except for MgO, were cytotoxic (LDH and WST-1 assay). ZnO, and to lesser extent SiO₂, induced significant DNA damage (Fpg-comet), while SiO₂ and carbon black were the most potent in causing glutathione depletion. DNA damage by TiO₂ was found to depend on sample processing conditions. Interestingly, application of different TiO₂ and ZnO particles revealed no relation between particle surface area and DNA damage. Our results indicate a potential hazard of several food-related nanoparticles which necessitate investigations on the actual exposure in humans.     

Induction of unscheduled DNA synthesis by chemical mutagens in testicular cells of the mouse in vitro

Testicular cells of male mice were isolated, and the incorporation of tritium labeled thymidine into the DNA of the cells was estimated after exposure to various chemical mutagens. The normal semiconservative DNA synthesis was suppressed by the addition of hydroxyurea. Thirteen compounds were tested. Unscheduled DNA synthesis (UDS) was stimulated by ethyl methanesulfonate (EMS), methyl methanesulfonate (MMS), N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and triaziquone, and, to a lesser extent, by 4-nitroquinoline 1-oxide (4-NQO), mitomycin C, ICR-191 and nitrogen mustard (HN-2). No thymidine incorporation could be estimated after incubation of the cells with 9 aminoacridine, hydroxyurethane, -naphthylamine, 2-acetylaminofluorene (AAF) nor with N-hydroxy-2-acetylaminofluorene (N-OH-AAF).Parts of these investigations were presented in the poster session at the sixth annual meeting of the EEMS in Gernrode, Democratic Republic of Germany 1976     

Maté attenuates DNA damage and carcinogenesis induced by diethylnitrosamine and thermal injury in rat esophagus

Drinking hot maté has been associated with risk for esophageal cancer in South America. Thus, the aims of this study were to evaluate the modifying effects of maté intake on DNA damage and esophageal carcinogenesis induced by diethylnitrosamine (DEN) and thermal injury (TI) in male Wistar rats. At the initiation phase of carcinogenesis, rats were treated with DEN (8 × 80 mg/kg) and submitted to TI (water at 65 °C, 1 ml/rat, instilled into the esophagus). Concomitantly, the animals received maté (2.0% w/v) for 8 weeks. Samples of peripheral blood were collected 4 h after the last DEN application for DNA damage analysis. At weeks 8 and 20, samples from esophagus and liver were also collected for histological and immunohistochemical analysis. Maté significantly decreased DNA damage in leukocytes, cell proliferation rates in both esophagus and liver and the number of preneoplastic liver lesions from DEN/TI-treated animals at week 8. A significant lower incidence of esophageal papillomas and liver adenomas and tumor multiplicity was observed in the animals previously treated with maté at week 20. Thus, maté presented protective effects against DNA damage and esophageal and liver carcinogenesis induced by DEN.     

三种GC-1细胞DNA损伤模型的建立及比较分析

目的建立3种小鼠睾丸精原细胞株GC-1细胞DNA损伤模型并分析其异同。方法分别采用UVB辐照、D-半乳糖(D-Galactose,D-Gal)、博来霉素(bleomycin,BLM)刺激GC-1细胞不同时间,Western blot和免疫荧光法检测γ-H2AX表达及定位;免疫荧光法检测8-OHdG表达及定位;Western blot法检测p-p53和p21表达水平。结果UVB辐照和D-Gal处理后,γ-H2AX蛋白表达分别在4 h和6 h达高峰BLM刺激后,γ-H2AX蛋白表达逐渐上升且BLM浓度越高,其达到高峰时间越短。UVB辐照和BLM刺激后,胞核胞质内均有8-OHdG表达,且时间越长,核内表达越多;D-Gal处理后,8-OHdG主要表达在胞质,且在6 h达高峰。UVB辐照后,p-p53和p21蛋白表达不断上升,p21表达较滞后;D-Gal处理后,p-p53和p21表达分别在6 h和12 h达高峰;BLM刺激后,p-p53和p21蛋白表达呈同步上升趋势,BLM浓度越高,其达高峰时间越短。结论成功建立3种GC-1细胞DNA损伤模型,且D-Gal处理GC-1细胞DNA损伤较轻,而UVB辐照和BLM刺激DNA损伤较重。     

Methamphetamine induces DNA damage in specific regions of the female rat brain

Methamphetamine (METH) is a highly addictive psychostimulant that has been shown to produce neurotoxicity. Methamphetamine increases the release of dopamine by reversing the direction of monoamine transporter proteins, leading to the formation of reactive oxygen species in the brain. In this study, we examined the effect of METH on DNA damage in vivo using the single cell gel electrophoresis assay (comet assay) under two different conditions. Rats treated with multiple doses of METH (10 mg/kg × 4) showed significant levels of DNA damage in the nucleus accumbens and striatum, both dopamine‐rich areas. In contrast, a single dose of METH did not lead to significant levels of DNA damage in any of the dopamine‐rich brain regions that were tested. Overall, the results of our study demonstrate that METH produces greater oxidative DNA damage in brain areas that receive greater dopamine innervation.     

Gallic acid provokes DNA damage and suppresses DNA repair gene expression in human prostate cancer PC‐3 cells

Our earlier studies have demonstrated that gallic acid (GA) induced cytotoxic effects including induction of apoptosis and DNA damage and inhibited the cell migration and invasion in human cancer cells. However, GA‐affected DNA damage and repair gene expressions in human prostate cancer cells are still unclear. In this study, we investigated whether or not GA induces DNA damage and inhibits DNA repair gene expression in a human prostate cancer cell line (PC‐3). The results from flow cytometric assay indicated that GA decreased the percentage of viable PC‐3 cells in a dose‐ and time‐dependent manner. PC‐3 cells after exposure to different doses (50, 100, and 200 μM) of GA and various periods of time (12, 24, and 48 h) led to a longer DNA migration smear (comet tail) occurred based on the single cell gel electrophoresis (comet assay). These observations indicated that GA‐induced DNA damage in PC‐3 cells, which also confirmed by 4,6‐diamidino‐2‐phenylindole dihydrochloride staining and DNA agarose gel electrophoresis. Alternatively, results from real‐time polymerase chain reaction assay also indicated that GA inhibited ataxia telangiectasia mutated, ataxia‐telangiectasia and Rad3‐related, O⁶‐methylguanine‐DNA methyltransferase, DNA‐dependent serine/threonine protein kinase, and p53 mRNA expressions in PC‐3 cells. Taken together, the present study showed that GA caused DNA damage and inhibited DNA repair genes as well as both effects may be the critical factors for GA‐inhibited growth of PC‐3 cells in vitro. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 579–587, 2013.     

Cell-specific oxidative DNA damage induced by estrogen in rat testicular cells in vitro

17 alpha-Ethinylestradiol (EE) can induce oxidative DNA damage in terms of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in rat testicular cells by an apparent estrogen receptor-mediated mechanism. We investigated differential susceptibility to EE in cell sub-populations from rat testes and the role of rat 8-oxo-guanine DNA glycosylase (rOGG1). Isolated rat testicular cells were incubated with EE concentrations ranging from 0.1 to 1000 nM. Single strand DNA breaks and oxidised purines as fapyguanine glycosylase (FPG) sensitive sites were assessed by the comet assay. In the total cell population and in round haploid cells, oxidised purines showed a bell-shaped concentration-response relationship with a maximally increased levels at 10 nM EE, whereas, no significant effects were seen in diploid, S-phase or tetraploid cells. The mRNA level of rOGG1 in testes cells was unaffected by EE, whereas, baseline levels were higher than in liver tissue and similar to colon tissue.     

Evaluation of DNA damage induced by norcantharidin in human cultured lymphocytes

Norcantharidin (NCTD) is currently used in the treatment of several cancers such as leukemia, melanoma and hepatoma. The mechanism of action of NCTD is suggested to involve induction of apoptosis of cancer cells via production of reactive oxygen species. In this study, the genotoxic effect of different concentrations of NCTD (1, 10 and 20?μm) in human lymphocytes was investigated using sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) assays. The results revealed that NCTD significantly increased the rate of SCEs (p?<?0.05) in a dose-dependent manner. In addition, NCTD significantly increased the number of high-frequency cells (SCEs?≥?8, p?<?0.05). However, NCTD did not have any significant effect on the rate of CAs (p?>?0.05). In addition, no significant differences were detected in the mitotic index or proliferative index at examined doses (up to 20?μm). In conclusion, NCTD is genotoxic to human cultured lymphocytes as measured by SCE assay.