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ABSTRACT: Patulin (PAT) is a fungal secondary metabolite commonly present in apples and apple products. In the present study, PAT was evaluated for its genotoxic, cytotoxic and cytostatic effects to human peripheral blood lymphocytes by using the cytokinesis-block micronucleus cytome (CBMN Cyt) assay. Lymphocyte cultures were treated with PAT at the following concentrations, 0.1, 0.3, 0.5, 1.0, 2.5, 5.0, and 7.5 μM, as well as 0.5 μM mitomycin c (MMC) as a positive control and dimethyl sulfoxide (DMSO) as a vehicle control. PAT was found to induce nucleoplasmic bridges (NPBs) at 5.0 and 7.5 μM concentrations (P < 0.05), apoptotic cells at 0.1, 1.0, 5.0 μM (P < 0.05), 7.5 μM concentrations (P < 0.01) and necrotic cells at 0.3 and 2.5 μM (P < 0.05), 5.0 and 7.5 μM (P < 0.01) concentrations in human lymphocytes. The 2.5, 5.0, and 7.5 μM PAT concentrations also led to a clear decrease in the nuclear division index (NDI) (P < 0.05). PAT caused a significant dose-dependent increase in the number cells of NPBs, in the frequency of apoptotic and necrotic cells, and a significant dose-dependent decrease in the NDI values in lymphocytes. These results indicate that PAT at high concentrations is genotoxic, cytotoxic and cytostatic in cultured human lymphocytes.
Mycotoxin Research 11/2012;
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ABSTRACT: Micronuclei (MN) in blood lymphocytes were determined in 31 male workers occupationally exposed to lead (Pb), zinc (Zn), and
cadmium (Cd) and 20 control workers matched for age and smoking habits. Exposed workers have higher MN mean values than control
workers (p<0.01). In exposed workers, blood Pb concentrations were also significantly higher than in control workers (p<0.001), but the mean concentrations of Zn and Cd in the blood were not statistically significant compared to the controls
(p>0.05). These results suggest that lead may be genotoxic and the human lymphocyte micronucleus test can be used to assess
genotoxic effects that result from occupational exposures.
Biological Trace Element Research 04/2012; 83(2):97-102. · 1.92 Impact Factor
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ABSTRACT: Acromegaly is a syndrome characterized by a sustained elevation of circulating growth hormone and insulin-like growth factor-1 (IGF-1). Insulin-like growth factor-1 is a potent mitogen and has a role in the transformation of normal cells to malignant cells. This study aims to evaluate the spontaneous micronucleus (MN) frequency by using the cytokinesis-block MN assay to determine genetic damage in the lymphocytes of patients with acromegaly. The study was carried out in 20 patients who had active acromegaly and in 20 age- and sex-matched healthy controls. The MN values were measured in binucleated cells obtained from mitogen-stimulated lymphocytes of patients and control subjects. The distribution of binucleated cells with 1, 2, 3, or more MNs was also measured. We found significantly higher MN frequency values in the lymphocytes of acromegalic patients than in those of the control subjects (2.23 ± 0.68 vs 1.03 ± 0.54, P = .001). The MN frequency increased with increasing IGF-1 levels of acromegalic patients (P = .036, R = 0.47). We observed that the number of binucleated cells with 2 MNs was higher for the majority of patients with acromegaly than for control subjects. Furthermore, the receiver operating characteristic curve (area under the curve = 0.914, P < .0001) was calculated to assess the discriminative power of the MN frequency. Our results indicate that increased MN frequency in the lymphocytes of patients with acromegaly may reflect genomic instability and this increased MN frequency may be associated with elevated levels of circulating growth hormone and IGF-1.
Metabolism: clinical and experimental 05/2011; 60(11):1620-6. · 2.59 Impact Factor
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ABSTRACT: Polycystic ovary syndrome (PCOS) has recently been linked with genomic instability and DNA damage. The aim of this study was to test genomic damage in women PCOS, using two different methods for assessing damage in both chromosome and base level. The study was performed on 36 newly diagnosed women with PCOS and 29 healthy women as controls. The micronucleus (MN) analysis used as a biomarker of chromosomal/DNA damage was performed in peripheral lymphocytes by cytokinesis-block method. 8-hydroxydeoxyguanosine (8-OHdG) levels used as a reliable marker of oxidative DNA damage were measured in plasma using an ELISA kit. We found that MN frequencies obtained from lymphocytes of the women with PCOS were significantly higher than those of controls (4.1 +/- 1.0 vs. 2.1 +/- 0.6, P = 0.001), whereas, no differences in 8-OHdG level were found between the patients with PCOS and controls (0.5 +/- 0.3 vs. 0.5 +/- 0.2, P = 0.858). These findings indicate that women with PCOS seem to have increased genomic instability, but do not appear to have oxidative DNA damage despite the increased oxidative stress associated with PCOS.
Gynecological Endocrinology 02/2010; 26(8):590-5. · 1.58 Impact Factor
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ABSTRACT: The objective of the current study is to determine the effects of regular wrestling exercise oxidative DNA damage and antioxidant parameters. The findings of the current study have shown that 8-hydroxy-2'-deoxyguanosine (8-OHdG) obtained from wrestlers in basal status were significantly lower than those of sedentary (p = .001). In contrast, Nitric oxide (NO) and Paraoxonase-1 (PON1) were remarkably higher in wrestlers in basal status than those of sedentary (respectively, p = .001, p = .024). While the NO of wrestlers increased immediately after a 1.5-h exercise compared with those before exercise (p = .002), no differences were found between before and immediately after a 1.5-h exercise in 8-OHdG and PON1 (respectively, p = .777, p = .408). Statistically significant correlations were found between the NO and PON1 in the wrestlers in basal status (r = .671, p = .002). In conclusion, our study suggests that wrestling exercise for a healthy life is important in that it reduces DNA damage as well as enhancing antioxidant parameters.
Pediatric exercise science 02/2010; 22(1):60-8. · 1.71 Impact Factor
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ABSTRACT: The trisomy 21 (Ts21) or Down's syndrome (DS) phenotype is assumed to occur primarily by the expression/overexpression of some genes encoded by the extra chromosome 21. It has recently been shown by AgNOR staining that babies with Ts21 have more AgNOR area (more NOR proteins) and more RNA content in their peripheral blood mononuclear cells (PBMCs) than those of controls. The aim of this study was to test whether or not the nuclear proteins content of PBMCs from trisomy 21 babies/infants is higher than that of the controls.
For this purpose, flow cytometric measurement of the stained PBMC nuclei was used. Nuclei from PBMCs was isolated and stained with propidium iodide and fluorescein isothiocyanate (PI/FITC) for DNA and protein estimation, respectively.
Mean nuclear protein content of Ts21's (N = 30, mean age = 3.46 +/- 3.05 years old) PBMCs was found statistically higher than that of the controls (N = 33, mean age = 3.79 +/- 1.93 years old) (P = 0.005, nonparametric Mann-Whitney U test for two independent variables). This means that the average nuclear protein content of PBMC from Ts21 infants is higher than that of the controls. Furthermore, there is a moderate negative correlation between the ages of the studied DS patients and the protein content in the nuclei of their PBMCs (Linear regression analysis: P = 0.002, r = -0.55). This correlation is not found with controls (P = 0.186, r = -0.24).
We have concluded that average protein content of PBMCs' nuclei from DS infants is higher than that of the controls, decreasing significantly with age.
Cytometry Part B Clinical Cytometry 04/2008; 74(2):128-32. · 2.53 Impact Factor
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ABSTRACT: Structural chromosomal aberrations have been described in various types of human leukemia. The micronucleus technique provides a measure of both chromosome breakage and chromosome loss. The present study investigated micronucleus (MN) frequency in mitogen-stimulated peripheral blood lymphocytes from 20 newly diagnosed and untreated leukemia patients: 4 with acute lymphoblastic leukemia (ALL), 10 with acute myeloid leukemia (AML), and 6 with chronic lymphocytic leukemia (CLL). The mean MN frequency for untreated patients was 3.65 +/- 1.47 in ALL, 3.55 +/- 1.24 in AML, 3.03 +/- 1.05 in CLL. No differences in MN frequency were seen between leukemia types ALL, AML, and CLL (P = 0.503). The mean basal MN frequency for all patients, regardless of leukemia type, was 3.41 +/- 1.19, which was significantly higher (P = 0.001) than that of 20 age-matched control subjects, 1.87 +/- 0.75. Although no significant relationship was found between age and MN frequency in patients with leukemia (r = 0.050; P = 0.835), the MN frequency in the lymphocytes of healthy control increased regularly and significantly with age (r = 0.531; P = 0.016). These data indicate that the increased baseline MN frequency in lymphocytes of untreated patients with leukemia may reflect genomic instability or deficiency of DNA repair capacity. MN enhancement in this disease may thus be a consequence of the disease process.
Cancer Genetics and Cytogenetics 02/2008; 180(2):140-4. · 1.39 Impact Factor
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ABSTRACT: Exposure to asbestos minerals has been associated with a wide variety of adverse health effects including lung cancer, pleural mesothelioma, and cancer of other organs. Many of the regions of Turkey have asbestos deposits. People in Doğanli village - one of these regions - have been environmentally exposed to chrysotile asbestos since they were born. In this study the effects of asbestos on micronucleus (MN) frequencies of inhabitants exposed to chrysotile asbestos have been examined. Thirty subjects who had been environmentally exposed to chrysotile asbestos and living in Doğanli village, and 25 controls were studied to assess the MN frequency. The control group was selected from healthy individuals with no exposure to asbestos and living in similar geographic conditions to Doğanli village. Peripheral blood samples were collected from each subject and cultured for MN assay. Cytochalasin-B was added to lymphocyte cultures for evaluation of MN in binucleated (BN) cells. The differences between those exposed to chrysotile asbestos and controls were not statistically significant in terms of BN cells with MN (p > 0.05). There was not a significant relationship between MN frequencies and age, sex, smoking, both in chrysotile asbestos-exposed subjects and in controls (p > 0.05). Although the detection of calcified pleural plaques found in the inhabitants has indicated environmental exposure to chrysotile asbestos, our results show that chrysotile asbestos was not an inducer of MN in subjects exposed to chrysotile asbestos.
International Journal of Environmental Health Research 03/2007; 17(1):45-51. · 0.86 Impact Factor
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ABSTRACT: The aim of the present study was to determine whether or not the phytohemagglutinin (PHA)-activated proliferation and average RNA content in peripheral blood mononuclear cells (PBMC) of Down syndrome (DS) patients change with age.
Stimulated portion of PBMC and total RNA levels in these cells after 72 h of PHA stimulation from 38 DS patients were compared with 28 age-matched healthy controls using flow cytometric measurement.
Decreased ratio of PBMC from DS patients undergoes mitogenic stimulation with age (r = -0.84, P = 0.000). This decrease is not observed in the cells of control individuals (r = 0.03, P = 0.869). Stimulated PBMC in infants with DS have higher level of RNA contents compared to controls (Z = 2.227, P = 0.026). While RNA content in mitogen-stimulated PBMC of DS decreased progressively and significantly with age (r = -0.70, P = 0.000), no significant age-related change in RNA content was found among the cells of healthy individuals in the range of 0-27 year old (r = 0.275, P = 0.157, P > 0.05).
Age-dependent decreases in mitogen-activated proliferation ratio and average RNA content of PBMC from DS patients appear as regular events. These results may contribute to the explanation of the immune deficiency seen in DS patients since the PHA-stimulated cells are principally T-lymphocytes. This is the first report on the decrease in PHA-stimulated proliferation ratio (stimulability) and RNA level in PBMC of DS patients in relation to age.
Cytometry Part B Clinical Cytometry 02/2007; 72(1):43-8. · 2.53 Impact Factor
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ABSTRACT: Cadmium (Cd) is a toxic heavy metal that has been classified as a human carcinogen by the International Agency for Research on Cancer. The genotoxic effects of cadmium oxide (CdO) were investigated in cultured dog lymphocytes after a short-term oral CdO administration by the micronucleus (MN) test. The dogs were given 10 mg CdO/kg body weight per day for 3 and 28 d, respectively group I (n = 7) and group II (n = 6). Blood samples were collected at the beginning of feeding and at 4 and 29 d after Cd administration and cultured for 72 h. Whereas no significant increase in the MN frequency in group I was observed (p = 0.398), a significant MN induction with CdO was found in group II (p = 0.028) when compared with initial MN frequencies of dogs in both groups. Our results suggest that CdO might be directly and/or indirectly genotoxic after a monthly oral administration of CdO in dogs.
Biological Trace Element Research 10/2006; 112(3):241-6. · 1.92 Impact Factor
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ABSTRACT: Trisomy 21 or Down syndrome (DS) is the most common genetic cause of mental retardation associated with the immunologic and other known defects. Extra chromosome 21 of DS patients contains an average of 40 extra copies of rRNA genes and the in vivo regulation of these genes' activity is not known. Because over 80% of total cellular RNA is rRNA, the measurement of total cellular RNA provides information on rRNA content. The aim of this work was to determine whether or not the additional chromosome 21 causes any increase in total cellular RNA content in mononuclear cells from peripheral blood (PBMNCs) of these patients and whether or not this content is modified with age.
PBMNCs of 48 patients with DS and 48 healthy controls were studied. RNA content of isolated PBMNCs was evaluated by flow cytometric measurements.
Average RNA content of younger DS patients' cells was significantly higher than that of healthy controls (P=0.003). Furthermore, the RNA content decreased significantly with increasing age of DS patients (r=-0.377, P=0.008) in the range of 0-26 year old, whereas no significant relationship was found between age and PBMNCs' RNA content of healthy controls in the same range of ages.
RNA content of PBMNCs from DS patients decreases rapidly with age. This is the first work on the age-dependent decrease of the RNA content in PBMNCs of DS patients.
Cytometry Part B Clinical Cytometry 02/2006; 70(1):24-8. · 2.53 Impact Factor
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ABSTRACT: Regulation of nucleolus organizer region (NOR) expression in trisomy 21 (Down syndrome [DS]) cells is not fully explained. This work compared NOR expression on metaphase chromosomes in gradiently stimulated lymphocytes from DS patients with those from healthy controls.
Conventional peripheral blood culture (72 h) and chromosomal preparation procedures were used except that blood samples from each individual were cultivated in the same but gradiently increasing concentrations (0.37, 0.75, 1.48, and 2.21 ml) of phytohemagglutinin (PHA) per 100 ml of medium. One hundred consecutive metaphases per concentration were analyzed for scoring the means of the active NORs bearing chromosomes (AgNOR+ chromosome) per individual and per concentration.
In contrast to healthy controls (n=24), AgNOR+ chromosomal number in lymphocytes from 30 DS patients increased in concordance to the gradient of PHA concentration in the culture medium.
DS lymphocytes do not downregulate their NOR expression in the limit of control cells. This in vitro result may serve as a clue for the explanation of the DS phenotype due to the wasted energy in producing unnecessary rRNA transcripts and AgNOR proteins in utero during organogenesis. These results also indicate that precautions must be used in routine work of NOR evaluation/interpretation in DS lymphocytes.
Cytometry Part B Clinical Cytometry 08/2005; 66(1):36-9. · 2.53 Impact Factor
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ABSTRACT: In 1991, reported that therapeutic ultrasound (US) did not induce sister chromatid exchanges (SCEs) in patients whereas, in 1984, reported that each of 10 patients exposed to therapeutic US had a statistically significant increase in SCEs. The present study was planned to investigate if there was chromosomal damage resulting from therapeutic US by using a micronucleus (MN) method, and to counter the lack of reports in this area over the past 10 years. A total of 20 female volunteers were included in the study; 10 of them with low back pain (mechanical low back pain and facet syndrome) were treated with US and 10 healthy cases constituted the control group. Patients with low back pain received 10 sessions of US therapy at an intensity of 2 W/cm(2) and a frequency of 1 MHz for 10 min and patients in the control group received sham US therapy for 10 min. Peripheral blood taken before and after the fifth and tenth applications of US therapy was cultured for MN frequencies both for the treatment and the control groups. The scores of MN assessed before the therapy were compared with those at the end of the fifth session and the end of the tenth session in the treatment and the control groups. Pretreatment, end of the fifth session and end of the tenth session MN frequencies were compared between the treatment and the control groups. There was no statistically significant difference in MN frequencies between pretreatment and fifth session or pretreatment and tenth session in both groups. Nor was there any significant difference in the MN frequencies of the treatment and control groups between pretreatment, fifth session and tenth session evaluations. In conclusion, we observed that therapeutic US did not induce increases in MN frequency, which are a sign of cytogenetic damage.
Ultrasound in Medicine & Biology 05/2004; 30(4):545-8. · 2.29 Impact Factor
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ABSTRACT: Narrow-band UVB (311 nm) lamps (TL01) are being increasingly used for phototherapy of psoriasis and other dermatoses, for their excellent effect compared with broad-band UVB sources and photochemotherapy. It is acknowledged that the TL01 lamp is probably two to three times more carcinogenic per minimum erythema dose than broad-band UVB, but the cumulative dose is considerably less than broadband UVB sources. Micronucleus (MN) test is used to detect both clastogenic (breaking) and aneugenic (abnormal segregation) effect of physical/chemical agents on chromosomes. The aim of this study is to evaluate MN frequencies in mitogen-stimulated lymphocytes of narrow-band UVB-treated patients.
Frequency of micronuclei in 72 h cultivated/mitogen-stimulated lymphocytes of 36 patients (age 7-73 years, mean+/-SD: 25.33+/-18.54) have been evaluated at pretreatment and after 20, 40, 60 sessions of narrowband UVB treatment.
While the beginning MN frequency +/-SD (%) was 1.07+/-0.63, it increased to 1.47+/-0.92, 1.47+/- 0.77, 1.41+/-0.31 corresponding, respectively, to 20, 40, 60 sessions. These sessions reciprocally correspond to 0.85+/-0.23, 2.97+/-0.72, 5.68+/-1.46 J/cm(2) doses of narrow-band UVB. Difference of MN frequency was statistically significant (P=0.002). Significant differences have been observed between the initial MN frequency and after that of 20, 40, 60 sessions (P=0.001, 0.004, 0.002, respectively).
The results of this study show that narrow-band UVB treatment causes a detectable chromosome damaging effect.
Photodermatology Photoimmunology and Photomedicine 05/2004; 20(2):81-5. · 1.30 Impact Factor
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ABSTRACT: Ochratoxin A (OTA( a nephrotoxic and carcinogenic mycotoxin, was investigated to examine its potency to induce micronuclei (MN) in cultured human lymphocytes. Lymphocyte cultures were treated for the last 48 h with OTA at concentrations of 25 μM, 10 μM, 1 μM, 100 nM, 10 nM, 1 nM, and 100 pM and absolute ethanol. At the highest concentration, OTA was found to induce MN in cytokinesis-blocked lymphocytes (p < 05). The 25 μM OTA concentration also led to a clear decrease in the percentage of binucleated cells, probably due to cytotoxicity. OTA at the other concentrations tested did not induce MN frequency. These results indicate that a high concentration of OTA is genotoxic in cultured human lymphocytes.
Food / Nahrung 02/2003; 47(1):33 - 35.
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ABSTRACT: Ochratoxin A (OTA), a nephrotoxic and carcinogenic mycotoxin, was investigated to examine its potency to induce micronuclei (MN) in cultured human lymphocytes. Lymphocyte cultures were treated for the last 48 h with OTA at concentrations of 25 microM, 10 microM, 1 microM, 100 nM, 10 nM, 1 nM, and 100 microM and absolute ethanol. At the highest concentration, OTA was found to induce MN in cytokinesis-blocked lymphocytes (p < 0.05). The 25 microM OTA concentration also led to a clear decrease in the percentage of binucleated cells, probably due to cytotoxicity. OTA at the other concentrations tested did not induce MN frequency. These results indicate that a high concentration of OTA is genotoxic in cultured human lymphocytes.
Food / Nahrung 02/2003; 47(1):33-5.
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ABSTRACT: PUVA describes the treatment of patients with psoralens plus an exposure to a source of UV light of 320-400 nm (UVA). Contradictory results have been reported on the chromosomal damage of PUVA when assayed by sister chromatid exchange (SCE) method. Micronucleus (MN) test is used to detect both clastogenic (breaking) and aneugenic (abnormal segregation) effect of physical/chemical agents on the chromosomes. No data have been found on the MN formation in the cells of PUVA treated patients. Frequency of micronuclei in 72 hours cultivated/mitogen-stimulated lymphocytes of patients have been evaluated at zero time and after 20, 40, 60 sessions of PUVA treatment. While the beginning MN frequency was approximately 0.22% (n=23), it raised to approximately 0.32 (n=23), approximately 0.42 (n=14) and approximately 0.53% (n=10) corresponding respectively to 20, 40 and 60 sessions. These sessions correspond reciprocally to 54+/-23, 172+/-48, 300+/-61 joules/cm2 of UVA and 13, 26, 39 mg/kg of 8-metoxypsoralen (8-MOP). While large interindividual variances were apparent, highly significant differences have been observed between initial MN frequency and after that of the 20, 40 and 60 sessions, (p = 0.000, p = 0.004, p = 0.005, reciprocally, Wilcoxon two-related samples test). The coefficient of correlation between MN frequency and UVA doses starting from zero to 60 sessions of treatment has been found as r = 0.61. This indicates a significant relationship between UVA doses and MN frequencies. However, MN inducibility and synergistic property of 8-MOP with UVA should be taken into account. Gradual MN increase during different sessions of PUVA treatment shows that--once appeared--a part of MN at least persist in the cells of patients from a few days to a few weeks. Smoking as a confounding factor seems to increase MN frequency (p = 0.053, Mann-Whitney U-test) in the beginning population, taken as the control population. This is the first report on the kinetics of MN formation during different sessions of PUVA treatment. Based on our results, we concluded that PUVA treatment causes a detectable chromosome damaging effect on the relatively profound cells/tissues of its human users. Therapists should be careful with its use, especially on the patients who may be more susceptible to carcinogenesis (e.g. immunosuppressed and/or elderly subjects).
The Tohoku Journal of Experimental Medicine 10/2002; 198(1):11-21. · 1.24 Impact Factor
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ABSTRACT: Some mycotoxins produced by microfungi are capable of causing disease and death in animals and humans. In the present study, the mycotoxin citrinin (CTN) was evaluated for its genotoxic effects to human peripheral blood lymphocytes from six different individuals. Lymphocyte cultures were treated for 48 h with CTN at six different concentrations between 10 and 100 microM. Lymphocyte cultures were also incubated with 0.1 microM mitomycin c (MMC) as a positive control, and 0.5% absolute ethanol as a vehicle control.CTN caused a significant concentration-dependent increase in micronucleus (MN) frequency in human lymphocytes. At the 60 microM, 80 microM and 100 microM concentrations, CTN was found to induce MN in cytokinesis-blocked lymphocytes in comparison with negative controls (P = 0.014). All the CTN concentrations also led to a clear decrease in the percentages of binucleated/mononucleated cells (P = 0.014). These results indicate that CTN at high concentrations is genotoxic in cultured human lymphocytes.
Journal of Applied Toxicology 27(4):337-41. · 2.48 Impact Factor
