The antioxidants,vitamin A and E but not vitamin C and melatonin enhance the proapoptotic effects of irinotecan in cancer cells in vitro

Irinotecan is one of the camptothecin analog which has been shown to have a broad spectrum of antitumor activities against various malignancies. The aim of this study was to evaluate the effect of vitamin A, C, E and melatonin on proapoptotic activity of irinotecan in human cancer cells in vitro. We observed that irinotecan induced apoptosis in all types of analyzed cell lines when used as a single agent. Combination of selected antioxidants with various doses of irinotecan (7.5–60 μM) resulted in significant increase in apoptotic cell death in A549 and HT29 cancer cell lines. The highest killing efficiency was observed after co-incubation of the cells with irinotecan and vitamin A (10 μM), or vitamin E (25 μM), respectively. The addition of vitamin C and melatonin to irinotecan treatment did not promote increase in killing of cancer cells. Our results indicate that some antioxidants can enhance the proapoptoic activity (properties) of irinotecan in human cancer cells in vitro. These findings may be supportive for the optimization of therapeutic efficacy of irinotecan treatment.     

Genotoxicity of irinotecan and its modulation by vitamins A,C and E in human lymphocytes from healthy individuals and cancer patients

Many patients being treated for cancer use dietary supplements, particularly antioxidants, in the hope of reducing the toxicity of chemotherapy or radiotherapy. However, clinicians should advise their patients against using antioxidant dietary supplements during chemotherapy. Irinotecan (CPT-11) is a common chemotherapeutic agent, but it causes side effects, including genotoxicity with damages the DNA of blood cells. The aim of this work was to evaluate the modulating effect of A, C and E vitamins on genotoxic activity of irinotecan (CPT-11) and to analyse the efficacy of DNA repair in lymphocytes of both patients with diagnosed colorectal carcinoma and healthy individuals in vitro. In healthy donors’ cells CPT-11 did not exert a strong, genotoxic effect, both in the presence of vitamins and without them. In turn, a statistically significant increase of DNA migration in the comet tails was noted in patients’ lymphocytes. The presence of vitamins A, C and E in incubation solutions acted synergistically, increasing the level of DNA lesions in cells caused by the exposure of the material on tested irinotecan concentrations. Analysis of the efficacy of DNA repair, performed after 2 h of postincubation, showed the decrease of DNA percentage in comet tails in all experimental samples.     

The DNA-damaging potential of tamoxifen in breast cancer and normal cells

Tamoxifen (TAM) is a non-steroidal anti-estrogen used widely in the treatment and chemoprevention of breast cancer. TAM treatment can lead to DNA damage, but the mechanism of this process is not fully understood and the experimental data are often inconclusive. We compared the DNA-damaging potential of TAM in normal human peripheral blood lymphocytes and MCF-7 breast cancer cells by using the comet assay. In order to assess whether oxidative DNA damage may contribute to TAM-induced lesions, we employed two DNA repair enzymes: endonuclease III (Endo III) and formamidopyrimidine-DNA glycosylase (Fpg). The kinetics of repair of DNA damage was also measured. In order to evaluate the involvement of free radicals in the genotoxicity of TAM we pre-treated the cells with nitrone spin traps: DMPO and POBN. The use of common antioxidants: vitamin C, amifostine and genistein, helped to assess the contribution of free radicals. TAM damaged DNA in both normal and cancer cells, inducing mainly DNA strand breaks but not alkali-labile sites. The drug at 5 and 10 μM induced DNA double strand breaks (DSBs) in lymphocytes and at 10 μM in MCF-7 cells. We observed complete repair of DSBs in cancer cells by contrast with incomplete repair of these lesions in lymphocytes. In both types of cells TAM induced oxidized purines and pyrimidines. Incubation of the cells with nitrone spin traps and antioxidants decreased, with exception of amifostine in MCF-7 cells, the extents of DNA damage in both kinds of cells, but the results were more distinct in cancer cells. Our results indicate that TAM can be genotoxic for normal and cancer cells by free radicals generation. It seems to have a higher genotoxic potential for normal cells, which can be the result of incomplete repair of DNA DSBs. Free radicals scavengers can modulate TAM-induced DNA damage interfering with its antitumour activity in cancer cells.     

Direct‐oxidative DNA damage and apoptosis induction in different human respiratory cells exposed to low concentrations of sodium chromate

The mechanism of Cr(VI) genotoxicity has still not been elucidated. We used Fpg‐modified comet assay to assess direct‐oxidative DNA damage on human lung (A549) and bronchial (BEAS‐2B) cells exposed to 0.1, 0.5, 1.0 and 10 μm sodium chromate for 0.5, 1 and 4 h. Moreover we evaluated apoptosis by morphological analysis and caspase‐3 activity, also after 24 h. On A549 cells a time‐dependent DNA damage, expressed as tail DNA%, beginning from 0.5 μm was found. For oxidative DNA damage an induction after 30 min to 0.5 μm decreasing with time, and a time‐dependent increase at 10 μm was found, indicating for low Cr(VI) concentration the oxidative stress as the first event followed by direct DNA damage and for the highest concentration a time‐dependent increase in oxidative DNA damage. On BEAS‐2B cells DNA damage was induced within 1 h at 0.5–10 μm , without changes with time, showing that BEAS‐2B cells are able to resist to Cr(VI) genotoxicity. Early oxidative DNA damage at 0.1 μm decreasing with time was also found. Significant apoptosis was observed by morphological analysis in A549 cells and to a lower extent in BEAS‐2B at 10 μm . The exposure to 10 μm induced caspase‐3 activity after 4 h in BEAS‐2B and after 24 h in A549 cells. The findings show a higher responsiveness of A549 cells to genotoxic effect of Cr(VI) and early transient oxidative DNA damage in BEAS‐2B. The results emphasize the suitability of this experimental model to evaluate the early genotoxic response of different cells to non‐cytotoxic concentrations of Cr(VI) on target organ. Copyright © 2009 John Wiley & Sons, Ltd.     

Modulation of irinotecan-induced genomic DNA damage by theanine

The possible chemoprotective activity of theanine against irinotecan-induced genomic DNA damage towards mouse bone marrow cells was investigated. Chromosomal aberrations, DNA damage, micronuclei formation and mitotic activity were studied in the current study as markers of genomic damage. Oxidative DNA stress markers such as 8-hydroxydeoxyguanosine, lipid peroxidation, reduced and oxidized glutathione levels were assessed as a possible mechanism underlying this amelioration. Theanine was neither genotoxic nor cytotoxic in mice at doses equivalent to 30 or 60 mg/kg for 12 days. Pretreatment of mice with theanine significantly reduced irinotecan-induced genomic damage in the bone marrow cells and these effects were dose dependent. Irinotecan induced marked biochemical alterations characteristic of oxidative DNA stress, including increased 8-hydroxydeoxyguanosine, enhanced lipid peroxidation and reduction in the reduced/oxidized glutathione ratio. Prior administration of theanine ahead of irinotecan challenge ameliorated these oxidative DNA stress markers. Overall, this study provides for the first time that theanine has a protective role in the abatement of irinotecan-induced genomic damage in the bone marrow cells of mice that resides, at least in part, on its ability to modulate the cellular antioxidant levels and consequently protect bone marrow from irinotecan genotoxicity.     

A phase II trial of irinotecan in hormone-refractory prostate cancer

Irinotecan is a DNA topoisomerase I inhibitor that has a wide spectrum of activity against human tumors in both preclinical and clinical studies. To evaluate the efficacy of irinotecan in hormone-refractory prostate cancer, we conducted a phase II study in 15 men with metastatic, PSA-progressive disease after primary androgen deprivation. Irinotecan was administered at a dose of 125 mg/m2 weekly for four weeks followed by a two-week rest period; cycles were repeated every six weeks. Response was assessed by evaluation of serial changes in the serum PSA. None of fifteen patients had a decline in PSA of greater than 50%; eight patients had stable disease as a best response. None of three patients with measurable disease had a partial or complete response. Toxicity was primarily hematologic and gastrointestinal, with 40% of patients requiring dose modification due to granulocytopenia and 20% requiring intravenous fluid supplementation after development of diarrhea. There were no treatment-related deaths. We conclude that irinotecan in the dose and schedule used in this trial does not have significant activity against hormone-refractory prostate cancer.     

Assessment of genomic damage and repair on human lymphocytes by paint thinner in vitro

Paint thinners are organic-solvent complex mixtures frequently used by car painters around the world in industries and shops. Some studies have revealed the oxidative effect induced by thinner inhalation; however, its genotoxic effect is poorly studied. The aim of this study was to assess the cytotoxicity, genomic damage and DNA repair in vitro induced by commercial paint thinner 0.14 in human lymphocytes. Cytotoxicity was determined by cell-viability analysis with trypan blue after 4?h treatment with different thinner concentrations (0.025 to 1.2?µL/mL). Genomic damage was evaluated by means of the alkaline single-cell gel electrophoresis (SCGE; pH > 13) in treated cultures after 1?h with three low-cytotoxic thinner concentrations (0.05, 0.1 and 0.2?µL/mL). In order to evaluate the genomic DNA repair, one set of SCGE slides was prepared immediately after treatment, and another one was prepared after 4?h of liquid-holding recovery. A significant level of cytotoxicity was observed over the entire concentration range of paint thinner in lymphocytes (F?=?175.98; p?≤?0.001). In the SCGE % tail DNA assessment, a significant increase of lymphocyte genomic damage was evidenced (F?=?72.32; p?p?相似文献   

盐酸伊立替康的不良反应及其预防处理

伊立替康(irinotecan,CPT-11)是喜树碱的半合成衍生物,是选择性拓扑异构酶Ⅰ抑制剂,本品及其体内代谢物SN-38可诱导单链DNA损伤,从而阻断DNA复制,产生细胞毒作用。CPT-11于1998年获FDA批准用于标准化疗方案治疗后转移性结肠直肠癌复发和恶化的二线治疗;于2000年3月获FDA批准联合氟尿嘧啶(5-FU)和亚叶酸钙(CF)用于转移性结肠直肠癌的一线治疗。本品单药有效率在18%左右,联合5-FU和CF的有效率约为50%。CPT-11主要不良反应有迟发性腹泻、恶心、呕吐、中性粒细胞减少症、急性胆碱能综合征等,现就其不良反应的表现类型及预防处理方法进行概述。     

Genotoxicity of antiobesity drug orlistat and effect of caffeine intervention: an in vitro study

Context: Obesity is a major global health problem associated with various adverse effects. Pharmacological interventions are often necessary for the management of obesity. Orlistat is an FDA-approved antiobesity drug which is a potent inhibitor of intestinal lipases. Objective: In the current study, orlistat was evaluated for its genotoxic potential in human lymphocyte cells in vitro and was compared with that of another antiobesity drug sibutramine, presently withdrawn from market due its undesirable health effects. Caffeine intake may be an additional burden in people using anorectic drugs, therefore, further work is needed to be carried out to evaluate the possible effects of caffeine on orlistat-induced DNA damage. Materials and methods: Human lymphocytes were exposed to orlistat (250, 500 and 1000?μg/ml), sibutramine (250, 500 and 1000?μg/ml) and caffeine (25, 50, 75, 100, 125 and 150?μg/ml) to assess their genotoxicity by comet assay in vitro. In addition, lymphocytes were co-incubated with caffeine (50, 75 and 100?μg/ml) and a single concentration of orlistat (250?μg/ml). Results: Orlistat and sibutramine were genotoxic at all concentrations tested, sibutramine being more genotoxic. Caffeine was found to be genotoxic at concentrations 125?μg/ml and above. Co-treatment of orlistat with non-genotoxic concentrations (50, 75 and 100?μg/ml) of caffeine lead to a decrease in DNA damage. Discussion and conclusion: Orlistat can induce DNA damage in human lymphocytes in vitro and caffeine was found to reduce orlistat-induced genotoxicity.     

Vanadyl sulfate can differentially damage DNA in human lymphocytes and HeLa cells

Using the comet assay, we showed that vanadyl sulfate induced DNA damage in human normal lymphocytes and in HeLa cells. Vanadyl at 0.5 and 1 mM produced DNA single- and double-strand breaks (SSBs and DSBs) in lymphocytes, whereas in HeLa cells we observed only SSBs. Post-treatment of vanadyl-damaged DNA from lymphocytes with formamidopyrimidine-DNA glycosylase (Fpg), an enzyme recognizing oxidized purines, gave rise to a significant increase in the extent of DNA damage. A similar effect was observed in HeLa cells, but, using endonuclease III, we also detected oxidized pyrimidines in DNA of these cells. There were no differences in the extent of DNA damage in the lymphocytes and HeLa cells in the pH >13 and pH 12.1 conditions of the comet assay, which indicates that strand breaks, and not alkali-labile sites, contributed to the measured DNA damage. Study of DNA repair, determined in the comet assay as an ability of cells to decrease of DNA damage, revealed that HeLa cells retained the ability to repair vanadyl-damaged DNA induced at a ten-fold higher concentration than that in lymphocytes. Incubation of the cells with nitrone spin traps DMPO, POBN and PBN decreased the extent of DNA damage, which might follow from the production of free radicals by vanadyl sulfate. The presence of vitamins A, C or E caused an increase of DNA damage in HeLa cells whereas in lymphocytes such an increase was observed only for vitamin C. Our data indicate that vanadyl sulfate can be genotoxic for normal and cancer cells. It seems to have a higher genotoxic potential for cancer cells than for normal lymphocytes. Vitamins A, C and E can increase this potential.     

Genotoxicity of urethane dimethacrylate,a tooth restoration component

Urethane dimethacrylate (UDMA) is used in dental restorative materials in its polymeric form. However, the process of polymerization is usually incomplete and the monomers of UDMA can diffuse into the oral cavity and the pulp, reaching millimolar concentrations. In the present work we showed that UDMA at 0.1 and 1.0 mM decreased the viability of and induced DNA damage in lymphocytes in a concentration dependent manner, but it did not affect a plasmid DNA in vitro. UDMA at 1 mM induced apoptosis in lymphocytes. The lymphocytes exposed to UDMA were able to repair their DNA within 60 min. Analysis with DNA repair enzymes Endo III and Fpg showed that UDMA induced mainly oxidative DNA lesions. Vitamin C and chitosan decreased genotoxic effect of UDMA. Our results show that monomers of UDMA may exert pronounced cyto- and genotoxic effects in human lymphocytes and chitosan can be considered as a protection against such effects.     

A phase II trial of irinotecan in hormone-refractory prostate cancer

Irinotecan is a DNA topoisomerase I inhibitor that has a wide spectrum of activity against human tumors in both preclinical and clinical studies. To evaluate the efficacy of irinotecan in hormone-refractory prostate cancer, we conducted a phase II study in 15 men with metastatic, PSA-progressive disease after primary androgen deprivation. Irinotecan was administered at a dose of 125 mg/m² weekly for four weeks followed by a two-week rest period; cycles were repeated every six weeks. Response was assessed by evaluation of serial changes in the serum PSA. None of fifteen patients had a decline in PSA of greater than 50%; eight patients had stable disease as a best response. None of three patients with measurable disease had a partial or complete response. Toxicity was primarily hematologic and gastrointestinal, with 40% of patients requiring dose modification due to granulocytopenia and 20% requiring intravenous fluid supplementation after development of diarrhea. There were no treatment-related deaths. We conclude that irinotecan in the dose and schedule used in this trial does not have significant activity against hormone-refractory prostate cancer.     

Expression of domains for protein–protein interaction of nucleotide excision repair proteins modifies cancer cell sensitivity to platinum derivatives and genomic stability

Nucleotide excision repair (NER) is involved in the repair of DNA damage caused by platinum derivatives and has been shown to decrease the cytotoxic activity of these drugs. Because protein–protein interactions are essential for NER activity, we transfected human cancer cell lines (A549 and HCT116) with plasmids coding the amino acid sequences corresponding to the interacting domains between excision repair cross‐complementation group 1 (ERCC1) and xeroderma pigmentosum, complementation group A (XPA), as well as ERCC1 and xeroderma pigmentosum, complementation group F (XPF), all NER proteins. Using the 3‐(4,5‐dimethyl‐2 thiazoyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay and annexin V staining, we showed that transfected A549 cells were sensitized 1.2–2.2‐fold to carboplatin and that transfected HCT116 cells were sensitized 1.4–5.4‐fold to oxaliplatin in vitro. In addition, transfected cells exhibited modified in vivo sensitivity to the same drugs. Finally, in particular cell models of the interaction between ERCC1 and XPF, DNA repair was decreased, as evidenced by increased phosphorylation of the histone 2AX after exposure to mitomycin C, and genomic instability was increased, as determined by comparative genomic hybridization studies. The results indicate that the interacting peptides act as dominant negatives and decrease NER activity through inhibition of protein–protein interactions.     

Caspase-mediated pro-apoptotic interaction of panaxadiol and irinotecan in human colorectal cancer cells

Objectives Panaxadiol is a purified sapogenin of ginseng saponins that exhibits anticancer activity. Irinotecan is a second‐line anticancer drug, but clinical treatment with irinotecan is limited due to its side effects. In this study, we have investigated the possible synergistic anticancer effects of panaxadiol and irinotecan on human colorectal cancer cells and explored the potential role of apoptosis in their synergistic activity. Key findings The combination of panaxadiol and irinotecan significantly enhanced antiproliferative effects in HCT‐116 cells (P < 0.05). Cell cycle analysis demonstrated that combining irinotecan treatment with panaxadiol significantly increased the G1‐phase fractions of cells, compared with irinotecan treatment alone. In apoptotic assays, the combination of panaxadiol and irinotecan significantly increased the percentage of apoptotic cells compared with irinotecan alone (P < 0.01). Increased activity of caspase‐3 and caspase‐9 was observed after treating with panaxadiol and irinotecan. The synergistic apoptotic effects were supported by docking analysis, which demonstrated that panaxadiol and irinotecan bound two different chains of the caspase‐3 protein. Conclusions Data from this study suggested that caspase‐3‐ and caspase‐9‐mediated apoptosis may play an important role in the panaxadiol enhanced antiproliferative effects of irinotecan on human colorectal cancer cells.     

Irinotecan toxicity to human blood cells in vitro: relationship between various biomarkers

Toxic effects of the antineoplastic drug irinotecan on human blood cells at concentrations of 9.0 microg/ml and 4.6 microg/ml were evaluated in vitro. Using the alkaline and neutral comet assay significantly increased levels of primary DNA damage in lymphocytes were detected. The induction of apoptosis/necrosis, as determined by a fluorescent assay, was also notably increased. Cytogenetic outcomes of the treatment were assessed by the analysis of structural chromosome aberrations and fluorescence in situ hybridization. A significantly higher incidence of chromatid breaks and complex quadriradials was observed. Painted chromosomes 1, 2 and 4 were equally involved in translocations, but only the chromosome 1 was involved in the formation of quadriradials. Sister chromatid exchange analysis was performed in parallel with the analysis of lymphocyte proliferation kinetics. The higher concentration of irinotecan caused almost seven-time increase, while the lower one caused a five-time increase of the basal sister chromatid exchange frequency, accompanied with significant lowering of the lymphocyte proliferation index. Using the cytokinesis-block micronucleus assay, a dose-dependent increase in micronucleus frequency along with the formation of nuclear buds and nucleoplasmic bridges was noticed. Inhibitory effects of irinotecan on enzyme acetylcholinesterase (AChE) were studied in erythrocytes. An IC(50) value of 5.0 x 10(-7) was established. Irinotecan was found to be strong inhibitor of the acetylcholine hydrolysis and to cause a continuous decrease of catalytic activity of AChE. The results obtained on a single donor may contribute to the understanding of irinotecan toxicity, but further in vitro and in vivo studies are essential in order to clarify remaining issues, especially on possible inter-individual variability in genotoxic responses to the drug.     

Genotoxic effects of chlorpyrifos,cypermethrin, endosulfan and 2,4‐D on human peripheral lymphocytes cultured from smokers and nonsmokers

Pesticides often cause environmental pollution and adverse effects on human health. We have chosen four structurally different pesticides (endosulfan, an organochlorine pesticide; chlorpyrifos, an organophosphate insecticide; cypermethrin, type II pyrethroid insecticide, and 2,4‐dichlorophenoxyacetic acid, a chlorinated aromatic hydrocarbon acid pesticide) to examine and compare their effects on DNA damage in acutely cultured human lymphocytes by the comet assay. In addition, possible differences in response between smoking and nonsmoking subjects were also investigated. Venous blood samples were obtained from healthy male nonsmoker (n = 7) and smoker (n = 8) donors. Primary cultures of lymphocytes were prepared and test groups were treated with three different concentrations (1, 5, and 10 μM) of endosulfan, chlorpyrifos, cypermehrin, and 2,4‐D. DNA damage was assessed by alkaline comet assay. We determined an increase in the ratio of DNA migration in human lymphocyte cell cultures as a result of treatment with cypermethrin, 2,4‐D and chlorpyrifos at high concentration. Endosulfan had no significant genotoxic effect even at 10 μM concentration. We suggest that chlorpyrifos and cypermethrin are more potentially genotoxic than endosulfan and 2,4‐D. Our findings also indicate that the only significant DNA damage between smokers and nonsmokers was observed in the 2,4‐D‐treated group. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2010.     

Amelioration of melatonin on oxidative stress and genotoxic effects induced by cisplatin in vitro

In this study, we made an effort to evaluate the possible protective actions of melatonin on cisplatin-induced oxidative damage in mice brain homogenate and genotoxic effects in human lymphocytes under in vitro conditions. The tissue homogenate was divided into three parts. The first portion was kept as control treated with dimethyl sulphoxide (DMSO) (group 1) while the second and third portion were treated with 24 µg/g tissue cisplatin alone (group 2) and 24 µg/g tissue cisplatin in combination with 3?mM melatonin (group 3), respectively. We measured the oxidative stress biomarkers such as lipid peroxidation, 8-hydroxy 2′ deoxyguanosine (8-OHdG) and antioxidant parameters such as reduced glutathione, superoxide dismutase, glutathione peroxidase, and glutathione reductase in brain homogenate. Likewise peripheral venous blood was collected from healthy donors and human lymphocyte culture was done using karyotyping medium. Cultures were divided into three groups. Group 1 was the control i.e. lymphocytes treated with DMSO 5 µg/mL. In group 2, lymphocytes were treated with 2 µg/mL cisplatin and group 3 with a combination of 2 µg/mL cisplatin and 0.3?mM melatonin. Incubation of tissue homogenates with cisplatin elevated the malondialdehyde and 8-OHdG levels which were then reversed by melatonin. Reduction in antioxidant parameters with respect to corresponding controls were also restored by melatonin treatment. Furthermore, supplementation of melatonin was found to modulate the chromosome damage elicited by cisplatin which was determined using Giemsa (GTG) banding and karyotyping. These findings suggest that melatonin improves the cellular function and helps them to survive in the belligerent environment created by free radicals.     

Cantharidin induces DNA damage and inhibits DNA repair‐associated protein levels in NCI‐H460 human lung cancer cells

Cantharidin is one of the major compounds from mylabris and it has cytotoxic effects in many different types of human cancer cells. Previously, we found that cantharidin induced cell death through cell cycle arrest and apoptosis induction in human lung cancer NCI‐H460 cells. However, cantharidin‐affected DNA damage, repair, and associated protein levels in NCI‐H460 cells have not been examined. In this study, we determined whether cantharidin induced DNA damage and condensation and altered levels of proteins in NCI‐H460 cells in vitro. Incubation of NCI‐H460 cells with 0, 2.5, 5, 10, and 15 μM of cantharidin caused a longer DNA migration smear (comet tail). Cantharidin also increased DNA condensation. These effects were dose‐dependent. Cantharidin (5, 10, and 15 μM) treatment of NCI‐H460 cells reduced protein levels of ataxia telangiectasia mutated (ATM), breast cancer 1, early onset (BRCA‐1), 14‐3‐3 proteins sigma (14‐3‐3σ), DNA‐dependent serine/threonine protein kinase (DNA‐PK), O⁶‐methylguanine‐DNA methyltransferase (MGMT), and mediator of DNA damage checkpoint protein 1 (MDC1). Protein translocation of p‐p53, p‐H2A.X (S140), and MDC1 from cytoplasm to nucleus was induced by cantharidin in NCI‐H460 cells. Taken together, this study showed that cantharidin caused DNA damage and inhibited levels of DNA repair‐associated proteins. These effects may contribute to cantharidin‐induced cell death in vitro. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1135–1143, 2015.     

In vitro cytotoxicity and genotoxicity of Furia®180 SC (zeta-cypermethrin) and Bulldock 125®SC (β-cyfluthrin) pyrethroid insecticides in human peripheral blood lymphocytes

In the present study, human peripheral blood lymphocytes were exposed in vitro to 0, 6, 12, 18, 24, and 30?μg/mL Furia^®180 SC (zeta-cypermethrin) and 0, 6.3, 12.5, 18.8, 25, and 31.3?μg/mL Bulldock^®125 SC (β-cyfluthrin). Exposure to 32?µg/mL bleomycin for 24?h served as a positive control. The cytotoxic and genotoxic effects of each insecticide were analyzed using alkaline comet and trypan blue dye exclusion assays. DNA damage was evaluated through three genotoxicity parameters: tail length (TL), tail moment (TM) and tail intensity (TI). Furia^®180 SC and Bulldock^®125 SC pyrethroid insecticides and bleomycin significantly increased DNA damage in a concentration-dependent manner. Bulldock^®125 SC induced more DNA damage than Furia. Lymphocyte viability did not change after exposure to different concentrations of the two pyrethroid insecticides and bleomycin. Moreover, genotoxic results demonstrated that Furia^®180 SC and Bulldock^®125 SC insecticides caused in vitro DNA damage in human peripheral lymphocytes.