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In this study, toxic effects of the cypermethrin in Allium cepa L. cells were investigated. For this aim, we investigated the changes in pigment contents, antioxidant enzymes, mitotic index and chromosomal abnormalities as indicators of toxicity. The seeds were treated with different doses (1.5, 3.0, 6.0 ppm) of cypermethrin for 72 h. The result showed that there was a significant alteration in the tested parameters depending on treatment dose in the seeds exposed to cypermethrin when compared to the control group. Cypermethrin exposure significantly reduced the carotenoid, chlorophyll a and b pigments in all treatment groups. The activity of superoxide dismutase showed a concentration-time dependent increase and the maximum increase was observed on day 15 of treatment at 6.0 ppm cypermethrin exposure. The activity of catalase increased gradually with increasing cypermethrin concentration, but a soft decrease in CAT activity was decreased after 15 days of 1.5 ppm and 3.0 ppm cypermethrin treatment. In the roots treated with 1.5, 3.0, and 6.0 ppm cypermethrin, the level of malondialdehyde was about 1.8, 2.4, and 3.4 times higher than the control group, respectively. It was also found that cypermethrin has a mitodepressive action on mitosis, and the MI was decreased depending on the dose of cyprmethrin. All of the concentrations of cypermethrin induced chromosomal abnormalities and the most common abnormality observed in the present study was chromosome bridges. © 2011 Wiley Periodicals, Inc. Environ Toxicol 2012.

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n the present study, toxic effects of active substance thiamethoxam of the insecticide Eforia were investigated on Allium cepa L. For this aim, we used the germination percentage, root length, weight gain, malondialdehyde (MDA) level, frequency of micronucleus (MN), chromosomal aberrations (CAs), and mitotic index (MI) as indicators of toxicity. Also, the changes in the root anatomy of A. cepa seeds treated with thiamethoxam were examined. The seeds in all the treatment groups were treated with three different doses (100, 250, and 500 mg/kg) of thiamethoxam for 72 h. The results showed that there were significant alterations in the germination percentage, root length, weight gain, MDA level, MN, CAs, and MI frequency depending on application dose in the seeds exposed to thiamethoxam compared to control group. Thiamethoxam treatments significantly reduced the germination percentage, root length, and weight gain in all the treatment groups (P < 0.05). But, it caused an increase in MN and CAs formation (P < 0.05). It was also found that thiamethoxam has a mito-depressive action on mitosis, and the MI was decreased depending on the dose of applied-thiamethoxam (P < 0.05). About 100, 250, and 500 mg/kg doses of thiamethoxam significantly enhanced the lipid peroxidation and caused an increase in MDA levels at each dose treatment (P < 0.05). Some anatomical damages such as necrotic cell death, unclear vascular tissue, unclear epidermis layer, cell deformation, and unusual form of cell nucleus were observed by using light micrographs. Each dose of thiamethoxam caused severe toxic effects on A. cepa cells, and the maximum toxic effect was observed at the dose level of 500 mg/kg. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2011.

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Genomic instability is one of the main characteristics of malignant tumors, including HPV-induced cervical cancer. The aim of this study was to explore the use of assessing chromosome aberrations (CA) in peripheral blood lymphocytes as a biomarker for genomic instability in high-risk HPV-infected women with high-grade squamous intraepithelial lesions (HGSIL). A total of 120 women were recruited for this study, following cytology/colposcopy evaluation and HPV DNA detection. The study groups consisted of 30 HPV(+) women with histologically confirmed cervical intraepithelial neoplasia grade 2/3 and 30 HPV(+) women with carcinoma in situ (CIS). Two control groups, including 30 women HPV(−) and 30 women HPV(+), were recruited among women who were reported as cytology negative. Lymphocyte cell cultures were established for 52 hr, and 100 complete metaphase cells were evaluated per subject for CA analysis. The results show that women with CIS had significantly higher frequencies of both aneuploidy (0.67 ± 0.20 vs. 0.14 ± 0.08, P = 0.020) and tetraploidy (0.88 ± 0.23 vs. 0.17 ± 0.08, P = 0.013) in comparison with HPV(−) controls. These findings suggest the usefulness of peripheral blood lymphocytes to detect genomic instability associated with HPV-induced HGSIL. Environ. Mol. Mutagen., 2008. © 2008 Wiley-Liss, Inc.

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In this study, a synthetic pyrethroid insecticide, lambda-cyhalothrin (LCT), was administered to adult female albino rats (Wistar rats) by gavage dose of 6.12, 3.06, 0.8mg/kg b.w. repeated for 13 days at 48h intervals. The cytotoxic and genotoxic effects of LCT were investigated in bone marrow cells, using the structural chromosomal aberration (SCA) and micronucleus (MN) test systems. Mitomycin C (MMC) was also used as positive control (2mg/kg b.w.). All the doses of LCT increased the number of SCAs and the frequency of micronucleated erythrocytes, with respect to the control group. Only the highest dose of LCT significantly increased the MN frequency compared with control ( Formula Not Shown ). It was also observed that LCT caused a significant decrease in the number of polychromatic erythrocytes compared with controls ( Formula Not Shown ). These observations indicate the in vivo suspectibility of mammals to the genetic toxicity and cytotoxicity potential of LCT.

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In this study, the genotoxic and cytotoxic potential of lambda-cyhalothrin (LCT), a synthetic pyrethroid insecticide, was investigated in Wistar rat bone-marrow cells, using the structural chromosomal aberration (SCA) and micronucleus (MN) test systems. LCT was administrated to adult female albino rats as repeated i.p. doses of 6.12, 3.06, 0.8mg/kg BW for 13 days at 48h intervals. Mitomycin C (MMC) was used as a positive control (2mg/kg BW). All the doses of LCT increased the number of structural chromosomal aberrations and the frequency of micronucleated erythrocytes, compared with the control group. It was also observed that LCT caused a significant decrease in the number of polychromatic erythrocytes. Our results demonstrate that LCT has a clastogenic/genotoxic potential as measured by the bone marrow SCA and MN tests in Wistar rats.

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Mycotoxins are fungal secondary metabolites that can be found in contaminated food and feed. There is some evidence to suggest that certain mycotoxins may be mutagenic. Here, we investigate the genotoxicity of the mycotoxin moniliformin (MON) (3-hydroxycyclobut-3-ene-1,2-dione) in human peripheral blood lymphocytes using chromosomal aberration (CA), sister-chromatid exchange (SCE), and micronucleus (MN) analysis. Lymphocyte cultures were treated for 48 h with six different concentrations of MON between 2.5 and 25 μM. CA, SCE, and MN frequencies were significantly increased in a dose-dependent manner compared with the negative control. The mitotic, replication, and cytokinesis-block proliferation indices were not affected by treatment with MON. The results provide evidence to demonstrate that MON can exert cytogenetic effects in human cells in culture. Environ. Mol. Mutagen. 2009. © 2009 Wiley-Liss, Inc.

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Total and fractionated organic extracts from industrial effluents and Labe river water were tested for mutagenicity using the Ames test with TA98 strain and its YG derivatives (YG1021, YG1024 and YG1041) and cytogenetic analysis with human peripheral lymphocytes in vitro. The bacterial mutagenicity results showed a dose-dependent increase in numbers of TA98 revertants (10⁵) with effluent extracts and lower, but still significant, increase (10³) with river water extracts 6 km downstream. The further increase of YG revertants indicates the possible presence of nitroarenes and aromatic amines in the tested samples. In fractionated samples the significant mutagenicity was detected in two – polar acidic and polar basic – fractions, but the numbers of revertants in all effluent fractions were about one order of magnitude lower compared with total extracts results. The cytogenetic effect in human peripheral lymphocytes in vitro was not significant. The increase in chromosomal aberrations was not clearly dose-dependent and may reflect more the combination of toxic and clastogenic effects.

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The human biomonitoring (HBM) is an integral part of Environmental Health Monitoring System in the Czech Republic since 1994. Selected biomarkers of the internal dose (heavy metals, PCBs) and cytogenetic analysis of peripheral lymphocytes as a biomarker of the exposure/effect to/of environmental genotoxic factors are systematically followed up in the blood and urine of adults (blood donors), in children aged 8 to 10 years, and in the breast milk of nursing mothers. Selected outputs documented the declining trend of blood lead levels, with the recent reference value of 80 mg/l for men, and the rising trend of blood selenium levels in adults, but not in children. PCBs and chlorinated pesticides in human milk show a long-term downward trend, but still higher than in neighbouring countries. The frequency of aberrant cells revealed a downward trend, but the increase obtained in the last monitored period needs to be explained. Further HBM activities are required to demonstrate the corresponding trends and to reduce human exposure and health risks.

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Amoxicillin (AMO), a drug used in the treatment of infections caused by susceptible bacteria, has been evaluated for its ability to induce genotoxicity in human peripheral blood lymphocytes. The potential genotoxic effects of AMO were investigated in vitro by the sister chromatid exchange (SCE), chromosomal aberration (CA), and micronucleus (MN) tests. The cells were treated with 400, 600, 800, and 1,000 μg/ml AMO in the presence and absence of a metabolic activator (S9 mix), respectively. In this study, AMO did not induce SCEs or CAs in human peripheral blood lymphocytes both in the presence and absence of the metabolic activator. AMO concentration-dependently decreased the proliferation index (PI) in the absence of the metabolic activation for 24-hr treatment period. Mitotic index (MI) was generally found to have been reduced when compared with the negative control but not with the solvent control in cultures treated with AMO for 24 hr. AMO did not decrease the PI and MI in the presence of the metabolic activator. Furthermore, AMO neither induced the formation of MN nor decreased the nuclear division index in human peripheral blood lymphocytes both in the presence and absence of the metabolic activator. According to the present results, we suggest that AMO does not pose genotoxic risk for patients who are under therapy against bacterial infections. Environ. Mol. Mutagen., 2010. © 2009 Wiley-Liss, Inc.

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A technical herbicide containing isopropyl amine salt of glyphosate was tested for induction of chromosome aberrations (CA) and sister chromatid exchanges (SCE) in cultured bovine peripheral lymphocytes. Cultures were exposed to a glyphosate formulation at concentrations ranging from 28 to 1120μmol/l without and with metabolic activation. No clastogenic effect of the herbicide was found. Its genotoxic effect was confirmed in the SCE assay after 24h of incubation. A statistically significant elevation in SCE induction was observed in each of the donors after application of the product at doses ranging from 56 to 1120μmol/l. The highest concentrations (560 and 1120μmol/l) also caused reduction of mitotic and proliferation indices. In the 2h-assay with metabolic activation a statistically significant frequency of SCE was observed only in cultures treated with the agent at a concentration of 140μmol/l.

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The commercial herbicide with active element bifenox (principal tradename Modown) was tested for the evaluation of genotoxicity in cultured cow peripheral lymphocytes in vitro. Several cytogenetic endpoints as chromosome aberrations (CA), sister chromatid exchanges (SCE), mitotic (MI) and proliferation (PI) indices were investigated in different sampling times. To detect possible metabolic modifications in herbicide genotoxicity, the cultures for SCE determination were also treated with S9 fraction. Cultures of lymphocytes were exposed to the herbicide at concentrations of 25, 50, 250, 500 and 1000 μg/ml. A slight increase of CAs was found after exposure of this agent to doses ranging from 25 to 250 μg/ml for 24 h. In the CA assay no statistical significance was seen. Both higher doses (500 and 1000 μg/ml) caused a decrease of chromosome damage in comparison to the last active dose or control values correlated to induced cytotoxicity. Four concentrations (all except the highest one) of the herbicide were applied into cultures in SCE assays both with and without metabolic activation. Significant elevations of SCE were observed after applications of herbicide tested at doses of 250 and 500 μg/ml in each donor (P<0.001 and P<0.05, respectively) for 24 h. These concentrations also caused a statistically significant decrease in the MI and PI. Treatment for 48 h provided inadequate evidence for the genotoxic activity of the herbicide.

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The association of occupational exposure to 1,3-butadiene (BD) and induction of cytogenetic damage in peripheral lymphocytes was studied in 19 male workers from a monomer production unit and 19 control subjects from a heat production unit. The exposure to BD was measured by passive personal monitors. The following biomarkers were used: chromosomal aberrations (CA), sister chromatid exchanges (SCE), cells with a high frequency of SCE (HFC), micronuclei, comet assay parameters like tail length (TL) and percentage of DNA in tail [T (%)] and polymorphisms of GSTM1 and GSTT1 genotypes. BD exposure with a median value of 0.53 mg/m³ (range: 0.024–23.0) significantly increased (a) the percentage of cells with chromosomal aberrations in exposed vs. control groups (3.11% vs. 2.03%, P<0.01), (b) the frequency of SCE per cell (6.96 vs. 4.87, P<0.001), and (c) the percentage of HFC (19.9% vs. 4.1%, P<0.001). BD exposure had no significant effects on formation of micronuclei and on comet assay parameters. Effect of smoking was observed only for HFC in BD-exposed group. GSTM1 genotype affected chromosomal aberrations in exposed group, while GSTT1 genotype affected chromosomal aberrations in controls. No effect of GSTM1 or GSTT1 genotypes was observed on any other biomarkers used.

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This paper summarizes the experiences of the Czech Hygiene Service since the middle 1970s until the present time, using cytogenetic analysis as a biomarker of exposure. We have included a review of all the available scientific literature in Czech as well as in English, and have described the most important milestones in the history of the use of cytogenetic analysis in the Czech Republic. Details on the levels of occupational exposure and the corresponding observed frequencies of aberrant cells are provided. Furthermore, we discuss the interpretation of the cytogenetic findings in the context of occupational health and give several examples when the results of cytogenetic analysis provided the chief argument used to enforce improved working conditions and to establish safer maximum allowable concentrations.

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We analyzed chromosome aberrations, micronucleus frequency, mitotic index (MI), and nuclear division index (NDI) in peripheral lymphocytes of sheep subchronically exposed to the fungicide Euparen Multi (containing 50% tolylfluanid). Euparen Multi was administered by rumen sonde to group of Merino sheep (seven sheep/group) at 93mg/kg body weight (1/20 LD₅₀) daily for 28 days to assess its genotoxic effects. The frequencies of aberrant cells (ABC) in the experimental and control groups were 5.50±1.38% and 2.40±1.14%, respectively, and the increase in ABC in the treated group was significant ( Formula Not Shown ). Significantly increased numbers of chromatid breaks (5.67±1.21% against 2.40±1.14%; Formula Not Shown ), chromatid gaps (10.33±2.73% against 4.00±1.23%; Formula Not Shown ), and chromosome gaps (1.83±0.75% against 0.80±0.45%; Formula Not Shown ) and exchanges (3.17±1.94% against 0.20±0.45%; Formula Not Shown ) were observed in exposed animals in comparison to control animals. The frequency of micronuclei (MN) was 29.40±5.86 per 1000 binucleated cells in peripheral lymphocytes of sheep in the control group and 49.57±19.12 per 1000 binucleated cells in the treated group. A significant increase in the frequency of MN in peripheral lymphocytes also was observed between the two groups ( Formula Not Shown ). No statistical differences in MI and NDI values were found in the groups ( Formula Not Shown and 0.761, respectively). Thus, our results suggest that exposure to Euparen Multi may cause genome damage in somatic cells.

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Beauvericin, a naturally occurring contaminants of food and feeds, has been implicated in several mycotoxicoses; however, there is little information on its genotoxicity. Therefore, the genotoxic and cytotoxic effects of beauvericin in in vitro cultures of human lymphocytes were investigated with chromosome aberrations (CAs), sister-chromatid exchanges (SCEs), micronuclei (MN) as well as mitotic, proliferative and nuclear division indices. Beauvericin caused a significant concentration-dependent increase in chromosomal aberrations, sister-chromatid exchanges and micronuclei. It also significantly decreased the mitotic index at the two highest concentrations. However, no significant change in the proliferative and nuclear division indices was found. The results indicated that BEA is genotoxic to human lymphocytes in vitro.

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We investigated the cytogenotoxic effects of high frequency electromagnetic fields (HF-EMF) for 45 day and the effect of a recovery period of 15 day after exposure to EMF on bone marrow cells of immature and mature rats. The animals in treatment groups were exposed to 1800MHz EMF at SAR of 0.37W/kg and 0.49W/kg for 2h/day for 45 day. Two recovery groups were kept for a recovery period of 15 day without EMF after exposure to HF-EMF. Two control groups for both immature and mature rats were also included. Significant differences were also observed in chromosome aberrations (CA), micronucleus (MN) frequency, mitotic index (MI) and ratio of polychromatic erythrocytes (PCEs) in all treatment groups. The cytogenotoxic damage was more remarkable in immature rats and, the recovery period did not improve this damage in immature rats. Because much higher and irreversible cytogenotoxic damage was observed in immature rats than in mature rats, further studies are needed to understand effects of EMF on DNA damage and DNA repair, and to determine safe limits for environment and human, especially for children.

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Petroleum derivatives constitute a complex mixture of chemicals which contain well-known genotoxicants, such as benzene. Thus, chronic occupational exposure to such derivatives may be considered to possess genotoxic risk. In the present study, frequencies of sister chromatid exchange (SCE); aberrant cells, including numerical and structural chromosomal aberrations; and chromosome aberrations were investigated in peripheral blood lymphocytes from 30 exposed workers (15 smokers and 15 nonsmokers) and 30 controls (15 smokers and 15 nonsmokers). The exposed subjects were employed at 12 different petrol pumping stations in the city of Mersin, Turkey. Urinary phenol levels of exposed workers were found to be significantly higher than those of control subjects. Benzene exposure and cigarette smoking decrease the replication index and mitotic index. There is an interaction between benzene exposure and cigarette smoking for replication index and mitotic index. There is no interaction between cigarette smoking and benzene exposure for chromosomal aberrations. The results indicate that there are significant differences in SCE values in the exposed workers compared to the control individuals (P<0.01), but there is no difference between smokers and nonsmokers for SCE frequency (P>0.05). SCE frequency is higher in smokers than in nonsmokers.

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Purpose

The pattern and frequency of secondary chromosome abnormalities in t(14;18)-carrying non-Hodgkin lymphomas (NHL) were evaluated for differences in relation to histologic NHL subtype and patients’ outcome.

Methods

One hundred and forty-nine NHL patients with t(14;18) and complete cytogenetic, morphologic, and clinical information were selected.

Results

One hundred and twelve cases were follicular lymphoma (FL) and 37 were diffuse large B-cell lymphoma (DLBCL). One hundred and forty cases showed secondary aberrations (94%, median = 6.0). The most frequent were losses from chromosome arms 1p and 6q and +7 (26%). Loss from 1q, +7, and +12 were more frequent in DLBCL than in FL. Loss from 1p, Xp, and −16 were more frequent in FL grade 3 than in FL grades 1 and 2. Patients with <6.0 secondary cytogenetic aberrations had better prognosis than did those with a higher number of aberrations. Trisomy 21 was associated with shorter patient survival. FLIPI score, the number of secondary chromosomal aberrations, and +21 were all of independent prognostic value in Cox multivariate analysis. FL grade 1-3a patients that had received chemotherapy, showed a higher frequency of i(6p) and loss from 6q.

Conclusion

Secondary chromosomal aberrations showed some correlation with the morphologic subgroups of t(14;18)-NHL. Trisomy 21 and the presence of >6.0 secondary cytogenetic aberrations both correlated with shorter overall survival.

▼ In an attempt to clarify the controversy about sodium fluoride (NaF) clastogenicity, the induction of chromosome aberrations in Chinese hamster ovary cells (CHO) by NaF was investigated. Following a protocol used for screening chemicals for clastogenic activity, significant increases of aberrant cells were observed when cells were exposed to NaF for 4 h and harvested 8 h later. Cell-cycle kinetic studies demonstrated most cells were exposed in G₂ of the cell cycle. Smaller increases in aberrant cells were observed when cells were harvested 20 h later (most cells were exposed in G₁/S). The sensitivity of G₂ cells to NaF was investigated further, along with the induction of aberrations at low doses. The results indicated that G₂ cells are sensitive to NaF and the percent of aberrant cells increased with dose and length of exposure. With a 3-h exposure until harvest, no statistically significant increase in aberrant cells was observed at doses below 10 μg/ml NaF. These data are consistent with a threshold for NaF-induced clastogenicity around 10 μg/ml, as has been proposed previously (Scott and Roberts, 1987). It thus may be predicted that clastogenic effects would not occur in humans exposed to the levels of fluoride that are present in drinking water or dentifrices. An understanding of the mechanism of NaF-induced clastogenicity would help to clarify this point. It has previously been reported that NaF inhibits DNA synthesis/repair. The types of aberrations, mostly deletions and gaps, the induction of endoreduplicated cells, the cell-cycle delay and the sensitivity of G₂ cells to NaF observed are similar to that reported in the literature for DNA synthesis/repair inhibitors like aphidicolin (APC). Similarities in the induction of aberrations by NaF and APC were confirmed in experiments with G₂ cells. Based on these results and those previously reported for NaF and APC, it is proposed that NaF-induced aberrations may occur by an indirect mechanism involving the inhibition of DNA synthesis/repair.

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Dextromethorphan (DMP) is an effective and widely used antitussive drug. While DMP has over a 50 year safe-marketing history, the only available genotoxicity data was an unpublished, negative Ames assay (Roche). Lack of a complete genotoxicity profile on DMP, specifically covering the chromosomal damage endpoint, prompted a regulatory request for an in vitro chromosome aberration assay. In accordance with EC and CPMP Guidance, we evaluated data for a number of chemicals with a structural relationship to DMP. DMP contains no structural alerts for genotoxicity or carcinogenicity using the Deductive Estimation of Risk from Existing Knowledge (DEREK) software tool, confirming the negative results obtained in the existing Ames assay. This is also consistent with the mostly negative genotoxicity and carcinogenicity data available on structurally related chemicals including morphine, codeine, nalbuphine, buprenorphine, naloxone, hydromorphone, levorphanol, and oxycodone. A state-of-the-science, in vitro chromosome aberration assay was also conducted, which demonstrated a lack of genotoxicity for DMP. The overall weight of evidence for DMP and its structural analogues, supports the conclusion that this class of phenanthrene-based chemicals, and DMP, in particular, are not genotoxic in vitro or in vivo, and do not represent a carcinogenic risk to patients.

▼ Bropirimine (U-54,461) is a novel compound which is being developed as a biological response modifier for use in treatment of neoplastic and viral disease. Compounds of this type exert their therapeutic effects by immuno-stimulation or other non-cytotoxic mechanisms. The purpose of the experiments described in this paper was to evaluate the hazard potential of this drug. Bropirimine was previously reported to be negative in the Ames Salmonella assay (Aaron et al., 1989a) and the in vitro UDS assay (Aaron et al., 1989b). In experiments reported here positive response was observed in a test for clastogenicity in vitro in CHO cells, but bropirimine was negative in the L5178Y mouse lymphoma TK^+^/^- assay. A subsequent experiment demonstrated the ability of bropirimine to induce HPRT mutations in CHO cells. Interestingly, evidence for induction of chromosome aberrations in the L5178Y cells by bropirimine was also obtained. While the reason for the apparent insensitivity of the L5178Y TK^+^/^- assay to bropirimine is unexplained by the experiments, it is clear that at high dose bropirimine is capable of clastogenesis in both CHO and L5178Y cells and can give rise to gene mutations in CHO cells but apparently not in L5178Y cells.

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Zearalenone (ZEN) is a potent estrogenic metabolite produced by some Fusarium species. No treatment has been successfully employed to remove ZEN contamination in foods. This study was conducted to evaluate the ability of hydrated sodium calcium aluminosilicate (HSCAS) to protect Balb/c mice against cytotoxicity and genotoxicity induced by ZEN. HSCAS was given via the oral route, either alone or simultaneously with a toxic intra-gastric dose of ZEN. The experimental approach comprised treatments of seven groups of mice. The first three groups received 400, 600 or 800mg/kg bw of HSCAS. Two experimental groups received, respectively, ZEN alone (40mg/kg bw, representing 8% of the LD₅₀) and ZEN in combination with HSCAS at 400mg/kg bw. The two control groups received distilled water and olive oil, respectively. The positive control groups received colchicine (4mg/kg bw) for the micronucleus assay and mitomycin C (1mg/kg bw) for the chromosome aberration test. Forty-eight hours after treatment, the femur and tibia were dissected out and analyzed. The results show that ZEN was cytotoxic and genotoxic to Balb/c mice, as indicated by the increase in the frequencies of micronucleated polychromatic erythrocytes (PCEMN) and of chromosomal aberrations in bone-marrow cells. The simultaneous intra-gastric administration of HSCAS with ZEN resulted in a reduction in the number of PCEMN and a decrease of the chromosomal aberration frequency, and an increase in the number of polychromatic erythrocytes (PCE) in bone-marrow cells, compared with those in the group treated with ZEN alone. It could be concluded that HSCAS itself was safe and efficient in the prevention of the toxic effects of ZEN in the gastrointestinal tract.

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Cadmium (Cd) is a non-essential element and is a widespread environmental pollutant. Exposure to cadmium can result in cytotoxic, carcinogenic and mutagenic effects. The aim of the current work was to evaluate the protective effect of Aquilegia vulgaris extract against the oxidative stress and the genotoxicity induced by Cd using the chromosomal aberrations in somatic and germ cells assay and random amplified polymorphism DNA (RAPD-PCR) analysis. Forty male Balb/c mice were divided into four groups including the control group, Cd-treated group and the groups treated with the extract alone or plus Cd. The results indicated that Cd increased serum ALT, AST, urea, LDH, CK, lipid peroxidation in liver tissue accompanied with a significant decrease in GPX and SOD. Cd also increased the number of chromosomal aberrations in bone marrow and spermatocytes including structural and numerical aberrations. Animals treated with the extract alone were comparable to the control regarding all the tested parameters. The extract succeeded in preventing or diminishing the oxidative stress and the clastogenic effects of Cd. It could be concluded that Aquilegia vulgaris extract is a promising protective agent against oxidative stress and genotoxicity during the exposure to Cd.

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The NAT1 gene exhibits polymorphisms in the non-coding polyadenylation region with a number of alleles. Of these alleles, NAT1^* 10 is responsible for increased NAT1 enzyme levels and is reported to be associated with increased risk for colorectal and bladder cancers. In view of the possible role of the NAT1 gene product in the metabolism of a number of cigarette smoke carcinogens, we tested the possibility that genetic variation in the NAT1 gene might also be associated with increased risk for lung cancer. Allelic variances of the NAT1 gene were analyzed in 45 lung cancer patients and 47 controls who were matched with respect to age, race and gender using restriction fragment length polymorphism (RFLP) analysis and allele-specific (AS)-PCR. Our results indicate that individuals who inherited the NAT1^* 10 allele had a 3.7-fold increased relative risk for lung cancer (95% CL = 1.2-16.0, p < 0.02). There was a 6.8-fold increase in relative risk for lung cancer associated with the inheritance of the NAT1^* 10 allele in younger individuals (< 60 years of age) compared to 2.2-fold increase in older individuals (> 60 years old) (OR = 6.8; 95% CL = 1.1-40.7, p < 0.01 and OR = 2.2; 95% CL = 0.5-11.1, p = 0.2, respectively). We have also applied the sensitive fluorescence in situ hybridization (FISH) tandem probe assay to elucidate the frequency of chromosome breakage among a subgroup of the studied individuals harboring the NAT1^* 10 allele (17 lung cancer patients, 17 smoking controls and 7 non-smoking controls). Our results indicate a significant increase (p < 0.001) in the frequency of chromosome breaks in lung cancer patients (mean ± SE per 100 cells = 1.45 ± 0.11) and in smoking controls (1.30 ± 0.13) compared to non-smoking controls (0.47 ± 0.07). Regression analysis indicated a highly significant positive correlation between the duration of smoking in years and the frequency of chromosome breaks in lung cancer patients (r = 0.62, p = 0.008), but not in smoking controls (r = 0.02; p = 0.91). These findings suggest that NAT1 polymorphism may be an important genetic determinant of lung cancer risk. In addition, these data provide a mechanistic link between the inheritance of the NAT1^* 10 allele and smoking-induced lung cancer. Given that the NAT1 enzyme can mediate activation and detoxication pathways for numerous carcinogens and given that this polymorphism is prevalent in the general population (20-50% frequency), it may play a significant role in influencing the outcome of a variety of environmental cancers.

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Bentonite and hydrated sodium calcium aluminsilicate (HSCAS) were added at a level of 0.5 % (w/w) to the diets containing 2.5 mg aflatoxins (AF) per kg diet and fed to male mature rats for 15 successive days. Aflatoxin alone significantly decreased feed intake and altered serum biochemical parameters of liver and kidney functions. Aflatoxin caused chromosomal aberrations in bone marrow cells. Bentonite or HSCAS did not alter any of the parameters measured. The addition of bentonite or HSCAS to the AF-contaminated diet diminished most of the deleterious effects of the aflatoxin. Pathological examinations of liver and kidney proved that both bentonite and HSCAS were hepatonephroprotective agents against aflatoxicosis. The cytogenetic findings demonstrated that the addition of bentonite or HSCAS to AF-contaminated diet suppressed chromosomal aberrations. These findings indicated that bentonite and HSCAS could diminished many of the adverse effect of dietary AF in rats. Copyright © 1998 John Wiley & Sons, Ltd.

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Sterigmatocystin (Stg) is closely related to the mycotoxin aflatoxin as a precursor in aflatoxin biosynthesis and classified as an IARC Group-2B carcinogen. The aim of this study was to investigate the efficacy of Egyptian montmorillonite (EM), a clay miniral, to adsorb Stg, to test the stability of the resulting complex under different conditions in vitro, and to utilize the Nile tilapia fish as an in vivo model to evaluate the protective effect of EM against Stg-induced toxicity and clastogenicity. In the in vitro study, four concentrations of EM (0.5, 1, 2 and 4mg/L aqueous solution) and three concentrations of Stg (5, 10 and 50μg/ml) were tested. The results show that EM had a high capacity of adsorbing Stg at different concentrations tested. The adsorption ranged from 93.1 to 97.8% of the available Stg in aqueous solutions. The complex was stable at different pHs at 37°C in different organic solvents. An in vivo experiment was conducted to evaluate the ability of EM to prevent the toxicity and chromosomal aberrations induced by Stg in the Nile tilapia fish. Fish received an intragastric dose of EM in corn oil (0.5mg/kg bw) with or without Stg (1.6μg/kg bw) twice a week for 4 weeks. Body weight was recorded during dosing, and blood and tissue samples were collected at the end of treatment. Stg residues were determined in fish tissue. The results show that Stg was toxic and clastogenic to fish as indicated by the significant decrease of body weight and the increase in frequencies of micronucleated red blood cells (MN RBC) and chromosomal aberrations in the kidney. The intragastric administration of EM combined with Stg to fish resulted in a reduction of the number of MN RBC and the frequency of chromosomal aberrations in the kidney compared with the group treated with Stg alone. It could be concluded that EM itself was safe and successful in the prevention of Stg toxicity and clastogenicity.

▼ The cytotoxic behaviour of 20 sesquiterpene lactones toward Chinese hamster ovary cells was examined. The structural pre-requisite for cytotoxicity was the α-methylene γ-lactone moiety. Certain sesquiterpene lactones caused chromosomal aberrations suggesting that DNA was the cellular target. The cellular target for most of these compounds, however, is probably not the nucleus and the cytotoxicity may be accounted for by Michael-type additions with sulphydryl groups of enzymes and other proteins.

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The genetic basis of infertility has received increasing recognition in recent years, particularly with the advent of assisted reproductive technology. It is now becoming obvious that genetic etiology for infertility is an important cause of disrupted spermatogenesis. Y-chromosome microdeletions and abnormal karyotype are the two major causes of altered spermatogenesis. To achieve biological fatherhood, intracytoplasmic sperm injection (ICSI) is performed in cases of severe infertility with or without genetic abnormalities. There is a concern that these genetic abnormalities can be transmitted to the male progeny, who may subsequently have a more severe phenotype of infertility. A total of 200 men were recruited for clinical examinations, spermiograms, hormonal profiles, and cytogenetic and Yq microdeletion profiles. Testicular biopsy was also performed whenever possible and histologically evaluated. Genetic abnormalities were seen in 7.1% of cases, of which 4.1% had chromosomal aberrations, namely Klinefelter’s mosaic (47XXY) and Robertsonian translocation, and 3.0% had Yq microdeletions, which is very low as compared to other populations. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) were significantly increased in men with nonobstructive azoospermia (NOA) as compared to severe oligoasthenozoospermia (P<0.0001), whereas testosterone levels were significantly decreased in men with microdeletions as compared to men with no microdeletions (P<0.0083). Low levels of androgen in men with microdeletions indicate a need to follow-up for early andropause. Patients with microdeletions had more severe testicular histology as compared to subjects without deletions. Our studies showed a significant decrease (P<0.002) in the serum inhibin B values in men with NOA, whereas FSH was seen to be significantly higher as compared to men with severe oligoasthenozoospermia (SOAS), indicating that both the Sertoli cells as well the germ cells were significantly compromised in cases of NOA and partially affected in SOAS. Overall inhibin B in combination with serum FSH would thus be a better marker than serum FSH alone for impaired spermatogenesis. In view of the genetic and hormonal abnormalities in the group of infertile men with idiopathic severe oligozoospermia and NOA cases, who are potential candidates for ICSI, genetic testing for Y-chromosome microdeletions, karyotype, and biochemical parameters is advocated. J. Clin. Lab. Anal. 22:29–38, 2008. © 2008 Wiley-Liss, Inc.

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The clastogenic activities of diepoxybutane and bleomycin were comparatively studied on prematurely condensed interphase chromatin and metaphase chromosomes of Chinese hamster ovary cells. The yield of chromosomal aberrations was distinctly higher in G2-premature chromosome condensation as compared to metaphase. Most notably, the clastogenic activity of bleomycin was visible in premature chromosome condensation after application of much lower final concentrations than necessary for induction of chromosome aberrations in metaphase. In addition, the different mechanisms of action of both clastogens were reflected by the aberration yield in GI and G2 immediately after exposure. While bleomycin induced aberrations throughout all stages of interphase, diepoxybutane did not induce aberrations in GI or G2. Though certainly not a routine system for genotoxicity testing, premature chromosome condensation analyses provide a powerful opportunity to demonstrate relationships between DNA damage and repair, and the production of chromosomal changes at the site of their formation.