Investigation of flurbiprofen genotoxicity and cytotoxicity in rat bone marrow cells

This study was performed to investigate cytogenetic effects of NSAID flurbiprofen which was used as active ingredient in some analgesic, antipyretic and anti-inflammatory drugs. Genotoxic effect of flurbiprofen was investigated using in vivo chromosome aberration (CA) test and random amplified polymorphic DNA–polymerase chain reaction (RAPD-PCR) test. Also, oxidative stress potential of flurbiprofen was determined by measuring total oxidant and antioxidant level which occurred with flurbiprofen treatment in rat peripheral blood. For these purposes, rats were treated with three concentrations of flurbiprofen (29.25, 58.50 and 117?mg/kg, body weight) in single dose at two different treatment periods (12 and 24?h). According to the results, flurbiprofen did not affect chromosome aberrations in rat bone marrow cells with CA test. In RAPD-PCR test, polymorphic bands were unaffected. Also, test substance did not change total oxidant and antioxidant status (except for 58.50 and 117?mg/kg, 12?h) and therefore it did not lead to significant increase on oxidative stress (again except 58.50 and 117?mg/kg, 12?h). However, flurbiprofen reduced to mitotic indexes and these reductions were dose-dependent for 12?h treatment. In summary, flurbiprofen did not show significant genotoxic effect. But it caused cytotoxicity in rat bone marrow cells.     

GC法测定香薷感冒滴丸中麝香草酚和香荆芥酚的含量

目的:建立气相色谱法测定香薷感冒滴丸中麝香草酚和香荆芥酚的含量。方法:色谱柱为 HP-17石英毛细管柱(HP50%PhMe Silicone,10m×0.25mm×0.25μm),柱初始温度130℃,停留14min,以20℃·min~(-1)速度一阶升温至220℃,停留36min。结果:麝香草酚在12.5～125.1μg·mL~(-1)(r=0.9998),香荆芥酚在21.5～215.2μg·mL~(-1)(r=0.9997)范围内有良好的线性关系;平均回收率分别为麝香草酚101.4%(RSD=2.7%),香荆芥酚98.7%(RSD=2.3%),重复性的 RSD 分别为麝香草酚2.3%,香荆芥酚2.0%。结论:本方法可靠、准确,专属性强,可以作为控制香薷感冒滴丸质量的方法。     

Cytogenetic effects of commercial formulations of deltamethrin and/or thiacloprid on wistar rat bone marrow cells

Deltamethrin (DEL) and thiacloprid (THIA) are two insecticides that are widely used in agriculture either separately or in combination. Studies on genotoxicity and cytotoxicity of TIA and the mixture of DEL and THIA insecticides have not been reported so far. Therefore, we investigated the cytotoxic and genotoxic effects of commercial formulations DEL and/or THIA in rat bone marrow cells, using mitotic index (MI), micronucleus (MN) and chromosome aberrations (CA) assay. In vivo cytokinesis‐block micronucleus ( CBMN) assay using cytochalasin‐B in bone marrow cells was performed for the first time in this study. Rats were orally gavaged with a single dose of DEL (15 mg/kg), THIA (112.5 mg/kg) or DEL + THIA (15 + 112.5 mg/kg) for 24 h (acute treatments), or DEL (3 mg/kg/day), THIA (22.5 mg/kg/day) or DEL + THIA (3 + 22.5 mg/kg/day) for 30 days (subacute treatments). A corn oil vehicle control group and cyclophosphamide (50 mg/kg) positive control group were also included. All DEL and/or THIA treatments significantly decreased MI and binucleated (BN) cell numbers, and significantly increased CA, as compared to the vehicle control group. The results of CBMN assay indicated that the combination of DEL and THIA for both treatment times and the 30‐day treatment with THIA alone caused a significant increase in micronucleus formation in BN cells. The present findings indicated the combined exposure of DEL and THIA showed genotoxic and cytotoxic effects more than those of individual exposure of DEL or THIA in rat bone marrow cells. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 524–531, 2013.     

Investigation of genotoxic effects of paraben in cultured human lymphocytes

Paraben is a phenolic derivative of benzoic acid extensively used as preservatives in food, pharmaceutical, and cosmetic industries due to its antimicrobial characteristics. The objective of this study was to evaluate the in vitro genotoxic effects of paraben in human lymphocyte cultures. Cells were analyzed by cytokinesis-block micronucleus (CBMN), chromosome aberration (CA), sister chromatid exchange (SCE), and comet tests. For CBMN, CA, and SCE assays, the human lymphocytes were isolated from healthy donors and incubated with 500, 250, 100, and 50?µg/mL of paraben for 24 and 48?h, and for comet assay, cells were exposed to 1000, 750, 500, and 250?µg/mL of paraben for an hour. Results showed that numbers of MN and SCEs were not significant in the cells exposed to paraben when compared to the solvent control. However, 500 and 250?µg/mL of paraben induced the CA after 24?h. Also, we observed a significant decrease in the cytokinesis-block proliferation index in cells exposed 250–500?µg/mL paraben for 24?h, and 100, 250, and 500?µg/mL for 48?h. The mitotic index was also decreased at all concentrations and periods. However, the proliferation index was statistically decreased at all concentrations after 48?h treatments. Only the highest concentration of paraben caused DNA migration (mean tail length) in human lymphocytes analyzed by Comet assay. Taken together, results indicated that paraben had cytotoxic effects and caused genotoxicity by affecting directly chromosomes and DNA in human lymphocyte cells in vitro, and may have genotoxic potential for human.     

Quantitation of specific myeloid cells in rat bone marrow measured by in vitro 35S-sulphate incorporation

A biochemical measurement which can be used for quantitation of specific early myeloid cells in rat bone marrow has been developed. This measurement consists of a rapid, simple assay for the in vitro quantitation of ³⁵S-sulphate incorporation into rat bone marrow cells. Incubation of bone marrow cells with ³⁵S-sulphate led to a time-dependent increase in radioactivity obtained in perchloric acid insoluble fractions of bone marrow cell suspensions. This incorporation was inhibited by cyanide and puromycin. Autoradiography has demonstrated the radiolabel to be specifically associated with immature cells of the myeloid series. The cells most active in this respect were eosinophils. When rats were treated with endotoxin, the rate of ³⁵S-sulphate incorporation was increased. Cell number measurements, using conventional histopathology and a Coulter Counter, demonstrated that endotoxin caused an initial release of mature granulocytes from the bone marrow. The regeneration of this mature population in the marrow was rapid, and was characterized by an increase in the number of immature cells and a concomitant increase in the rate of ³⁵S-sulphate incorporation measured in preparations of bone marrow cells in vitro. Furthermore, this response to endotoxin has demonstrated that Coulter Counting techniques can be used to distinguish specific populations of cells (e.g. mature granulocytes) within the bone marrow.     

The effect of titanium particles on rat bone marrow stem cells in vitro

In arthroplasty prostheses and dental implant, titanium is an excellent biocompatible material for its advanced physical qualities and better biocompatibility. However, it was reported that high ratios of titanium particles can be liberated due to the continual loading or articulation cycles of the implant. Because bone marrow stem cells (BMSCs) located adjacent to the implant are critical contributors to osseous tissue integrity, this study researched the influence of titanium particles on BMSCs’ viability, proliferation, and cell skeleton. In addition, the phagocytosis of titanium particles by BMSCs and expression of tumor suppressor protein p53 were also examined. It was found that exposure of BMSCs to titanium particles disrupted their viability and proliferation in vitro, which may due to the phagocytosis of titanium particles by BMSCs. Moreover, cell skeleton was destroyed and the p53 protein level increased as the titanium particles were added. For these results, it was concluded that titanium particles had a cytotoxic effect on BMSCs in vitro and would inhibit the bone formation around the implant.     

In vitro genotoxic and cytotoxic effects of some paraben esters on human peripheral lymphocytes

Parabens (PBs) are p-hydroxybenzoic acid ester compounds commonly employed as antimicrobial preservatives, mainly in food, cosmetic, and pharmaceutical products. The aim of the present study was to investigate the genotoxic and cytotoxic effects of some paraben esters (butyl paraben, propyl paraben, isobutyl paraben, and isopropyl paraben) on human peripheral lymphocytes, using in vitro sister chromatid exchange (SCE), chromosome aberration (CA), and cytokinesis-block micronucleus (CBMN) tests. Lymphocyte cultures were treated with four concentrations of PBs (100, 50, 25 and 10?µg/mL) for 24 and 48?h. Paraben esters significantly induced MN formations as compared to solvent control. Furthermore, butyl paraben and propyl paraben increased MN formations a concentration-dependent manner at 24 and 48?h. PBs increased the CA at 24 and 48?h. However, this increase was not meaningful for butyl paraben and isopropyl paraben at 48?h when compared with solvent control. Butyl, isobutyl, and isopropyl paraben significantly increased the SCE at 24 and 48?h. However, propyl paraben did not induce SCE meaningfully in both treatment periods. A significant decrease in the cytokinesis-block proliferation index and mitotic index was observed in cells exposed to all concentrations of PBs at 24 and 48?h. However, proliferation index was not affected at all concentrations of PBs after 24?h treatment, although it was decreased at the highest concentration of PBs at 48?h. It is concluded that all of the paraben esters used in this study have highly genotoxic and cytotoxic effects on human lymphocytes cells in vitro.     

Assessment of acetamiprid-induced genotoxic effects in bone marrow cells of Swiss albino male mice

Acetamiprid (ACE), a neonicotinoid insecticide, is widely used in agriculture either alone or in combination with other insecticides. A combined approach employing micronucleus test (MNT) and chromosomal aberrations (CA) assay was utilized to assess the genotoxic effects of ACE in bone marrow of Swiss albino male mice. Acetamiprid was administered i.p. daily at 4.6 and 2.3?mg/kg/day along with 3% gum acacia as negative control for 60 and 90?days and cyclophosphamide (50?mg/kg b.wt.) as positive control. ACE treatment resulted in a dose-dependent increase in the frequencies of micronuclei per cell and chromosomal aberrations in bone marrow cells. The increased micronuclei formation in total erythrocyte cells (immature PCEs and mature NCEs) was observed only at higher dose level (4.6?mg/kg b.wt.) administered for 90?days. The test also indicated the cytotoxic effect of higher dose level of pesticide by PCE/NCE ratio. The number of chromosomal aberrations were increased in the pesticide treated group compared to the negative control group, although significant increase was observed only in the group exposed to higher dose level of pesticide for both 60 and 90?days. Thus, daily exposure of ACE at a dose level of 4.6?mg/kg body weight for 60 and 90?days caused genotoxic and cytotoxic effects on the somatic cells of Swiss albino male mice.     

Reduction in fluoride-induced genotoxicity in mouse bone marrow cells after substituting high fluoride-containing water with safe drinking water

Treatment of mice with 15 mg l^?1 sodium fluoride (NaF) for 30 days increased the number of cell death, chromosomal aberrations (CAs) and ‘cells with chromatid breaks’ (aberrant cells) compared with control. The present study was intended to determine whether the fluoride (F)‐induced genotoxicity could be reduced by substituting high F‐containing water after 30 days with safe drinking water, containing 0.1 mg F ions l^?1. A significant fall in percentage of CAs and aberrant cells after withdrawal of F‐treatment following 30 days of safe water treatment in mice was observed which was highest after 90 days, although their levels still remained significantly high compared with the control group. This observation suggests that F‐induced genotoxicity could be reduced by substituting high F‐containing water with safe drinking water. Further study is warranted with different doses and extended treatment of safe water to determine whether the induced damages could be completely reduced or not. Copyright © 2011 John Wiley & Sons, Ltd.     

E838对小鼠骨髓细胞染色体的辐射防护作用

目的探讨E838对γ射线照射小鼠骨髓细胞染色体损伤的防护作用。方法将615小鼠,随机分为对照组、辐射对照组、E838组、炔雌三醇(EE3)组。E838组和EE3组分别腹腔注射E838和EE3,另两组给予等体积茶油,第3次给药24 h后进行剂量为1.5 Gy的137Csγ射线全身照射,观察其骨髓细胞染色体畸变率。结果 E838组、EE3组骨髓细胞染色体畸变与辐射对照组比较差异有统计学意义(P<0.01),E838组畸变细胞与EE3组比较差异有统计学意义(P<0.05)。结论 E838可降低辐射诱发的骨髓细胞染色畸变细胞数,对骨髓细胞染色体具有一定的辐射防护作用。     

Antigenotoxic effect of apigenin against mitomycin C induced genotoxic damage in mice bone marrow cells

The antigenotoxic effect of apigenin was studied against the genotoxic damage induced by mitomycin C on mouse bone marrow cells using sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) as parameters. Apigenin was studied at three different doses i.e. 10, 20 and 40 mg/kg b.w. and was found to be non-genotoxic at all the above three doses. Mitomycin C at 2 mg/kg b.w. was given along with the 10, 20 and 40 mg/kg bw of apigenin. A significant decrease in SCEs and CAs was observed, suggesting a protective role of apigenin against the genotoxicity of mitomycin C on mice bone marrow cells.     

Cytogenetic risk assessment of etoposide from mouse bone marrow

Increased clinical applications of the anticancer drug etoposide (a non-intercalative epipodophyllotoxin derivative) and the frequent induction of a second malignancy, particularly leukaemia, in post-etoposide-treated cancer survivors warrant detailed genotoxicity testing of etoposide. The genotoxicity test results available on etoposide are either primarily in in vitro test systems or in lower organisms after treatment with unusually high doses, or after chronic exposures, having little extrapolative value to humans. Therefore, a cytogenetic risk assessment study on etoposide in mouse in vivo was undertaken after a low dose (in accordance with the human therapeutic dose) single exposure. The cytogenetic toxicity of etoposide was assessed from bone marrow of mouse at three separate endpoints: chromosomal aberration and mitotic index studies at 24 h post-treatment and the micronucleus test (MNT) at 30 h post-treatment. The flame drying technique using colchicine, hypotonic sodium citrate, methanol-glacial acetic acid and Giemsa was followed for the preparation of slides for the metaphase chromosomal aberration and mitotic index studies and a simple technique was followed for the MNT. Although induction of chromosomal aberrations, excluding gaps, per 100 metaphases by 10 and 15 mg kg(-1) etoposide was not significant statistically, 20 mg kg(-1) of etoposide induced a significantly higher number of chromosomal aberrations in female (P < or = 0.01) and male (P < or = 0.05) mice. There was no significant change in the induced percentages of dividing cells by any of the doses of etoposide tested. The micronucleus induction also was not significant statistically with the lowest dose but it was significant in female (P 相似文献   

The delayed genotoxic effect of N-nitroso N-propoxur insecticide in mammalian cells.

The N-nitroso derivative of an extensively used insecticide, propoxur, consistently induced dose-responsive chromosome aberrations and sister-chromatid exchanges (SCEs) in Chinese hamster ovary (CHO-W8) cells. Further investigations indicated that post-treatment incubation with a regular 1.5-cell-cycle period did not offer an unbiased estimation of the genotoxicity of N-nitroso carbamate insecticides. The scale of chromosome aberration induction increased with extension of the post-treatment incubation period. Comparable phenomena were not found in CHO-AGT cells proficient for O(6)-methylguanine-DNA-methyltransferase. In CHO-W8 cells, pulsed-treatment of the insecticide in the 1st replication cycle showed higher SCE induction than in the 2nd cycle. Similar phenomenon was also found in SCE induced by N-nitroso derivatives from other carbamate insecticides including aldicarb, carbofuran and methomyl. Treated cells did not show significantly perturbed cell cycle progression until 12 h after treatment removal. Based on the above observations, the O(6)-methylguanine-DNA adduct is suggested to be the major lesion caused by the delayed genotoxic effect of N-methyl carbamate insecticides as described in this report.     

In vivo assessment of genotoxic potential of brown shammah (smokeless tobacco) in bone marrow cells of mice

This study was aimed to assess the genotoxicity of brown shammah (BS), a local form of smokeless tobacco, popular in Middle East countries including Yemen, Saudi Arabia and Sudan. The genotoxicity was explored using in vivo chromosomal aberration (CA), micronucleus (MN) and sperm abnormality (SA) assays. In addition, oxidative stress was also determined using various hepatic markers. Swiss albino mice were selected for the study, which were divided in to 5 groups of six animals each. They include, negative control (NC, received only vehicle) as well as positive control group (PC, received vehicle for 2 weeks followed by administration of cyclophosphamide, CP). Depending upon their dose, three BS treated animal groups were BS-100, 300 and 900 mg/kg. Doses of BS were obtained by suspending BS in 0.5% CMC (carboxy methyl cellulose) and orally administered once a day for 2 weeks. Significant augmentation of the average percentage of aberrant metaphase (AM), CA per cells and suppressed mitotic activity was observed on post administration of BS. In addition, BS increased the occurrence of MNPCEs (micronucleated polychromatic erythrocytes) formation, induced cytotoxicity and increased percentage of abnormal sperms as compared to NC. Moreover, BS also induced oxidative stress as the activities of hepatic superoxide dismutase (SOD) and glutathione (GSH) were reduced and malondialdehyde (MDA) content were increased by BS. Cyclophosphamide was utilized as clastogen, showed anticipated positive results and confirmed the sensitivity of test system. Therefore, it may be deduced from the study that the BS possesses genotoxic effects on mice bone marrow and germ cells in vivo.     

胎儿骨髓间充质干细胞的分离和培养

目的探讨胎儿骨髓间充质干细胞(mesenchymalstemcells,MSCs)的分离和培养条件。方法用DMEM培养液冲洗引产胎儿的骨髓腔,密度梯度离心法分离出其中的单个核细胞后,用含10%胎牛血清的DMEM/F12培养液,将细胞浓度调整到5×105个/ml,接种于12孔培养板中(1ml/孔),放在37℃、含体积分数为5%的CO2的饱和湿度培养箱中培养,48h后更换新鲜培养液,去除未贴壁细胞,以后每3d换液1次继续培养。当细胞铺满培养板底90%以上时,按常规方法进行细胞传代培养。结果原代培养的细胞接种后4h部分细胞开始贴壁,24h大量细胞贴壁并且胞浆伸出突起,变成梭形,培养10～14d后细胞融合成片铺满瓶底;传代培养的细胞1h即可贴壁,4h细胞开始伸展扩大,7～10d即可铺满瓶底。结论用密度为1.077g/ml淋巴细胞分离液作为分离液,密度梯度离心法分离培养的胎儿骨髓MSCs增殖力强,操作简单,是一种较好的分离和培养MSCs的方法。     

The genotoxic and antigenotoxic potential of the methanolic root extract of Glycyrrhiza glabra L. on human peripheral blood lymphocytes

Glycyrrhiza glabra L. (licorice) is one of the most important medicinal plants, which is widely used throughout the world both in traditional and contemporary medical industries. This study was undertaken to investigate the potential genotoxic activity of G. glabra methanolic root extract, and its possible antigenotoxic properties against mitomycin C (MMC)-induced DNA damage in in vitro chromosome aberrations (CAs) and cytokinesis-block micronucleus (CBMN) assays in human peripheral blood lymphocytes (PBLs). Lymphocytes were treated with 25, 50, and 100?µg/ml G. glabra methanolic root extract alone as well as in combination with MMC (0.1?µg/ml) for 24 and 48?h treatment periods. It was found that there were no statistically significant differences between the negative control and the groups treated with all concentrations of G. glabra root extract of alone (p?>?0.05), demonstrating the absence of genotoxic effects at both 24 and 48?h treatment periods. Besides, the co-treatment of G. glabra methanolic root extract and MMC significantly decreased the percentage of structural CAs and MN formation when compared with the culture treated with MMC alone (p?G. glabra versus MMC. We can state that this extract acts as an antagonist and markedly decreased MMC-induced cytogenotoxicity. In conclusion, the present results demonstrate that in the tested experimental conditions, G. glabra methanolic root extract is not genotoxic in cultured human PBLs and has also antigenotoxic activity against MMC, which is widely used in chemotherapy against cancer.     

Fluoride-induced genotoxicity in mouse bone marrow cells: effect of buthionine sulfoximine and N-acetyl-L-cysteine

A significant level of reactive oxygen species generation was observed in sodium fluoride (NaF) treated mouse bone marrow cells (BMCs). Reduced glutathione (GSH) as a free radical scavenger could be an important determining factor in F‐induced genotoxicity. We therefore attempted to monitor GSH to understand the mechanism of NaF‐induced genotoxicity. NaF was injected intra‐peritoneally in normal, buthionine sulfoximine (BSO) or N‐acetyl‐ l ‐cysteine (NAC) treated mice (n = 5). After 13 h of NaF‐treatment BMCs were collected to harvest them at the same divisional cycle and processed for analysis of cell cycle, induction of apoptosis and chromosomal aberrations (CAs). Level of GSH was also measured concomitantly. NaF induced significant CAs in all treatment groups except at 2.5 mg NaF kg^?1 body weight. BSO‐treatment alone induced significantly high frequency of CAs. BSO treatment prior to injection of 2.5–7.5 mg NaF kg^?1 b.w. was found to increase the frequency of CAs, significantly when compared with the positive control group, but the level was not significant in case of higher doses of NaF treatment (15 and 30 mg kg^?1 b.w.). NaF‐treated cells also showed a higher population of Annexin‐V positive cells. NAC pre‐treatment significantly reduced the extent of NaF‐induced CAs, which clearly indicates the involvement of GSH in the NaF response. However, further study is warranted to evaluate the low synergistic effect of BSO on higher doses of NaF‐induced CAs. Copyright © 2010 John Wiley & Sons, Ltd.     

The in vitro genotoxic and cytotoxic effects of remeron on human peripheral blood lymphocytes

Remeron (Mirtazapine) is an antidepressant drug which exerts its action by blocking presynaptic α-2-adrenergic receptors and postsynaptic serotonin types 2 and 3 receptors. In this in vitro analysis, human peripheral blood lymphocytes was treated by remeron (10, 25, 40 and 55 μg/mL) for 24 hours and 48 hours periods, then it was attempted to study of genotoxic and cytotoxic effects of the substance on human peripheral blood lymphocytes by some tests such as sister chromatid exchange (SCE), chromosomal abnormalities (CA) and micronucleus (MN) tests. Also proliferating effect of the substance was investigated. Remeron didn’t significantly cause chromosomal abnormalities and sister chromatid exchange while caused micronucleus at 40 μg/mL concentration and 24?h periodic time and increased proliferation index of the both 24 and 48 hours treated cells was decreased in a concentration manner. Also, exposing to the remeron for 24 and 48 hours leaded to a decrease in mitotic index and nucleus division index in the cells by concentration dependent manner. These findings showed that remeron did not have significantly genotoxic effects on human peripheral blood lymphocytes while it showed cytotoxic effects on the cells, which is the first report on genotoxic and cytotoxic properties of remeron.     

脑缺血大鼠骨髓间质干细胞移植后脑内分布与迁移

目的观察骨髓间质干细胞移植后在脑缺血大鼠脑内的存活、分布及迁移情况。方法Fieoll-Paque分离液梯度离心分离大鼠骨髓间质干细胞（rat bone mesenchymal stem cells，rMSCs），经体外培养扩增并流式细胞术鉴定；线拴法制作大鼠大脑中动脉闭塞（MCAO）脑局灶缺血模型，Hoechst33342标记细胞，分别通过静脉移植及立体定向局部移植到大鼠缺血侧纹状体。经过1、3、5周处死大鼠，取脑组织切片，在倒置荧光显微镜下观察细胞在脑内的存活、分布及迁移情况。结果应用梯度离心方法可以分离得到rMSCs，经过体外扩增可得到足够细胞数量用于移植，流式细胞术检测CD34、CD45表达阴性，CD29、CD90表达阳性。大鼠脑缺血后，无论静脉还是局部移植，rMSCs在脑内均能较长时间存活，移植细胞与宿主有很好组织相容性。静脉移植的细胞集中于脑缺血灶及其周围，缺血灶对侧脑组织移植的细胞较少（P〈0．05）；局部移植的细胞随着时间的推移向缺血灶不断迁移，分布在两侧大脑的差别都具有统计学意义（P〈0．05）。结论rMSCs通过静脉及立体定向两条途径进行移植后，能够在宿主缺血的脑中存活，向损伤部位迁移。rMSCs的这种迁移现象很可能与缺血灶的细胞信号改变有关，在临床上具有很大的潜在价值。     

The investigation of the genotoxic effects of fenarimol and propamocarb in mouse bone marrow in vivo

In this study, we aimed to evaluate the genotoxic effects of fungicides fenarimol and propamocarb which are used to protect crops from fungi. For this reason, bone-marrow micronucleus and chromosome aberration tests were carried out in Swiss albino mice. Mice were injected with four different doses of fenarimol and propamocarb intraperitoneally; 50, 100, 200 and 400 mg/kg b.w. Fenarimol did not induce any significant increase in micronucleated erythrocytes after 24, 36, and 48 h treatment but it decreased the ratio of polychromatic/normochromatic erythrocytes at all dose groups and sampling intervals. Fenarimol did not increase the number of chromosome aberrations significantly, but it reduced the mitotic index at the higher doses (P < 0.05). Propamocarb did not increase the frequency of micronucleated erythrocytes, but decreased the polychromatic/normochromatic erythrocytes ratio at all sampling intervals. Propamocarb increased only gaps in total chromosome aberrations, but when gaps were excluded, there were no significant differences in total aberrations between the control and dose groups (P > 0.05). Propamocarb also reduced the mitotic index compared with the negative control group (P < 0.001). Contributing these results, we can suggest that fenarimol and propamocarb are non-genotoxic in mouse bone marrow in vivo but have cytotoxic effects.