Frequency Of Sister Chromatid Exchanges Research Articles

Relationships between cytokine (IL-6 and TGF-β1) gene polymorphisms and chromosomal damage in hospital workers

Cytokine gene polymorphisms have been found to be associated with a pre-disposition to a variety of diseases, including inflammatory and cancer diseases. The present study evaluated the influence of six cytokine gene polymorphisms on the level of genomic damage observed in peripheral blood lymphocytes from hospital pathologists chronically exposed to low doses of different xenobiotics. Lymphocytes from 50 pathologists and 50 control subjects were recruited and analyzed in Sister Chromatid Exchange (SCE) and Chromosomal Aberrations (CA) assays. The frequencies of six cytokine gene polymorphisms and their relationships with the cytogenetic damage levels were also evaluated. The results indicated that significant differences were found between pathologists and controls in terms of SCE frequency (p < 0.001) and RI values (p < 0.001), as well as in terms of CA and cells with aberrations (p < 0.001). No associations were found between all analyzed cytokine gene polymorphisms and CA frequency in both pathologists and control groups. Vice versa, among pathologists, homozygote individuals for the IL-6 G allele showed a significantly (p = 0.017) lower frequency of SCE with respect to heterozygote subjects. Similarly, for TGFβ1 codon 10 locus, homozygote for T allele and heterozygote TC subjects showed a significantly (p = 0.021) lower frequency of SCE with respect to homozygote CC individuals. Among controls, no significant differences were found in the frequency of SCE between genotypes at all loci. Based on these results, we speculate that high circulating levels of a pro-inflammatory cytokine like IL-6 and lower levels of the immunosuppressant cytokine TGFβ1 could be associated directly with a longer duration and/or greater intensity of inflammatory processes, and indirectly with significantly higher levels of genomic damage.

The effect of thiacloprid formulation on DNA/chromosome damage and changes in GST activity in bovine peripheral lymphocytes

The potential genotoxic effect of thiacloprid formulation on bovine peripheral lymphocytes was evaluated using the comet assay and the cytogenetic endpoints: chromosome aberrations (CAs), sister chromatid exchanges (SCEs) and micronuclei (MNi). Whole blood cultures were treated with the insecticide at concentrations of 30, 60, 120, 240 and 480 μg mL−1 for 24, 48 h and/or 2 h of incubation. A statistically significant increase in the frequency of DNA damage, as well as in unstable chromosome aberrations (% breaks) were found after exposure to the insecticide at concentrations ranging from 120 to 480 μg mL−1 (P < 0.05, P < 0.01, P < 0.001). For the detection of stable structural chromosome aberrations (e.g., translocations) and numerical aberrations by the FISH method, three whole chromosome painting probes for bovine chromosomes 1, 5 and 7 (BTA1, BTA5 and BTA7) were used in our experiments. We observed numerical aberrations, but without any statistical significance. Regarding the sister chromatid exchanges, no significant elevation in the SCE frequencies was found after 24-h exposure to the insecticide. A dose-related response in the SCE induction was obtained in bovine cultures after the prolonged time of exposure (48 h) to thiacloprid formulation at concentrations ranging from 120 to 480 μg mL−1 in each donor (P < 0.05, P < 0.01), which was associated with a reduction of the PI (P < 0.05, P < 0.01). The insecticide failed to produce MNi; however, a significant reduction of CBPI was observed. Using real-time PCR, a decrease in the expression of bovine glutathione S-transferase M3 (GSTM3) was detected at the lowest dose. The higher concentrations of thiacloprid formulation caused an increase in the mRNA expression.

Baseline frequency of chromosomal aberrations and sister chromatid exchanges in peripheral blood lymphocytes of healthy individuals living in Turin (North-Western Italy): assessment of the effects of age, sex and GSTs gene polymorphisms on the levels of genomic damage

Background: The increased exposure to environmental pollutants has led to the awareness of the necessity for constant monitoring of human populations, especially those living in urban areas.Aim: This study evaluated the background levels of genomic damage in a sample of healthy subjects living in the urban area of Turin (Italy). The association between DNA damage with age, sex and GSTs polymorphisms was assessed.Subjects and methods: One hundred and one individuals were randomly sampled. Sister Chromatid Exchanges (SCEs) and Chromosomal Aberrations (CAs) assays, as well as genotyping of GSTT1 and GSTM1 genes, were performed.Results: Mean values of SCEs and CAs were 5.137 ± 0.166 and 0.018 ± 0.002, respectively. Results showed age and gender associated with higher frequencies of these two cytogenetic markers. The eldest subjects (51–65 years) showed significantly higher levels of genomic damage than younger individuals. GSTs polymorphisms did not appear to significantly influence the frequencies of either markers.Conclusion: The CAs background frequency observed in this study is one of the highest reported among European populations. Turin is one of the most polluted cities in Europe in terms of air fine PM10 and ozone and the clastogenic potential of these pollutants may explain the high frequencies of chromosomal rearrangements reported here.

GENOTOXICITY OF FORMALDEHYDE IN PERIPHERAL BLOOD LYMPHOCYTES AMONG PATHOLOGY LABORATORY WORKERS

Introduction: Formaldehyde (FA) is a chemical, traditionally used in pathology and anatomy laboratories as a tissue preservative. Many studies clearly indicated that FA can induce genotoxic effects in peripheral blood lymphocytes. Aim of work: to evaluate the genotoxic effects of formaldehyde among medical and paramedical personnel in The Histopathology Laboratory. Materials and Methods: The study was conducted in histopathology laboratory including 30 workers occupationally exposed to formaldehyde and 29 persons from other lab in kasr Al Aini hospital matching the exposed group for age, sex and socioeconomic status with no history of occupational exposure to formaldehyde. A questionnaire was done including inquiries about age, sex, occupational history and special habits. All participants were subjected to the following laboratory investigations: measuring DNA protein crosslink (DPC), sister chromatid exchange (SCE) and micronucleus (Mn) frequency in peripheral blood lymphocytes. Environmental monitoring of the work place was done to measure the level of FA at different place in the pathology lab. Results: This study showed statistically significant increase of DPC with significant increase in sister chromatid exchange (SCE) and micronucleus MN in peripheral blood lymphocytes. Conclusion: The studied group was exposed to formaldehyde level above the exposure limits recommended by NIOSH, ACGIH and OSHA with adverse health effects in the form of increase in DPC, SCE and Mn as genotoxicity biomarkers. These genotoxicity biomarkers are considered to play an important role in the carcinogenesis of FA.

In vitro and in vivo effects of melatonin on sister chromatid exchange in human blood lymphocytes exposed to hypoxia

Objective: Many studies have shown that melatonin (MLT) has an anti-genotoxic effect in various tissues and cell lines. The aim of this study was to investigate the anti-genotoxic effect of MLT on normal human peripheral lymphocytes by assessing sister chromatid exchange (SCE) in vitro and in vivo. Materials and methods: Cells were treated with 50 and 200 μM of MLT. The human volunteers (n = 20) for the in vivo study were administered a single dose of 3 mg MLT daily for 2 weeks. After sufficient time for its clearance, 1.5 mg of MLT daily was then administered to the same volunteers at same the period. Results: Our results demonstrated the anti-genotoxic effect of MLT in human blood lymphocyte in vitro and in vivo. In vitro, hypoxia increased the SCE frequency compared to the control and both doses of MLT significantly decreased the SCE frequency in the hypoxic cells (p < 0.001). In vivo, oral administration of 3 mg MLT significantly increased the frequency of SCE, yet a small increase of SCE by hypoxia was found. Oral administration of 1.5 mg MLT showed no DNA damage but it had an anti-genotoxic effect. Discussion and conclusion: MLT may prove useful for reducing the genotoxic effects of hypoxia in peripheral lymphocytes and suggest its possible role for ischemic diseases.

Assessment of HEMA and TEGDMA induced DNA damage by multiple genotoxicological endpoints in human lymphocytes

ObjectivesResidual unbound resin monomers of 2-hydroxyethyl methacrylate (HEMA) and triethylene glycol dimethacrylate (TEGDMA) are known to diffuse in the saliva and through dentin and pulp into the blood and may affect cellular integrity. The current study was performed to investigate the genotoxic potential of both monomers in distinctly lower concentrations than known to cause cytotoxic damage. MethodsLymphocytes from 10 healthy volunteers were treated with HEMA (10μM–1mM) and TEGDMA (1μM–100μM) for 24h. Cell viability, apoptosis and influence on cell cycle kinetics were assessed by flowcytometry. DNA damage was determined by the alkali version of the comet assay in combination with the FPG protein and by the cytokinesis-block micronucleus (CBMN) test. Additionally, the chromosome aberration (CA) test and sister chromatid exchange (SCE) test were performed. ResultsA slight decrease in cell viability was detected only at the highest concentration of TEGDMA. Genotoxic effects were measurable in the comet assay at 1mM of HEMA and 100μM of TEGDMA, with and without FPG protein, but not in the CBMN test or the cell cycle analysis. Contrary to these findings, a significant dose-dependent increase in the frequency of CAs and SCEs could be demonstrated in all tested concentrations. SignificanceThis is the first time clastogenic responses to HEMA and TEGDMA have been detected in concentrations distinctly lower than those reported for causing cytotoxic or even genotoxic effects. These findings underline the importance of using test batteries with different genotoxicological endpoints to describe the multiple effects of both resin monomers.

ATRX contributes to epigenetic asymmetry and silencing of major satellite transcripts in the maternal genome of the mouse embryo.

A striking proportion of human cleavage-stage embryos exhibit chromosome instability (CIN). Notably, until now, no experimental model has been described to determine the origin and mechanisms of complex chromosomal rearrangements. Here, we examined mouse embryos deficient for the chromatin remodeling protein ATRX to determine the cellular mechanisms activated in response to CIN. We demonstrate that ATRX is required for silencing of major satellite transcripts in the maternal genome, where it confers epigenetic asymmetry to pericentric heterochromatin during the transition to the first mitosis. This stage is also characterized by a striking kinetochore size asymmetry established by differences in CENP-C protein between the parental genomes. Loss of ATRX results in increased centromeric mitotic recombination, a high frequency of sister chromatid exchanges and double strand DNA breaks, indicating the formation of mitotic recombination break points. ATRX-deficient embryos exhibit a twofold increase in transcripts for aurora kinase B, the centromeric cohesin ESCO2, DNMT1, the ubiquitin-ligase (DZIP3) and the histone methyl transferase (EHMT1). Thus, loss of ATRX activates a pathway that integrates epigenetic modifications and DNA repair in response to chromosome breaks. These results reveal the cellular response of the cleavage-stage embryo to CIN and uncover a mechanism by which centromeric fission induces the formation of large-scale chromosomal rearrangements. Our results have important implications to determine the epigenetic origins of CIN that lead to congenital birth defects and early pregnancy loss, as well as the mechanisms involved in the oocyte to embryo transition.

Antigenotoxic potential of curcumin and carvacrol against malathion-induced DNA damage in cultured human peripheral blood and its relation to GSTM1 and GSTT1 polymorphism

The aerial application of malathion, a widely used organophosphate insecticide, has raised public concerns about its potential adverse health effects. We, therefore, studied the antigenotoxic potential of curcumin and carvacrol against malathion-induced DNA damage using sister chromatid exchange (SCE) as a biomarker of genotoxicity. To observe the antigenotoxic potential of curcumin and carvacrol, heparinized fresh blood from healthy individuals was treated with 30 μg/mL of malathion in the presence of curcumin and carvacrol. Curcumin at concentrations of 25 μg/mL and 50 μg/mL had significantly reduced (p < 0.05) the frequency of SCE as compared to malathion-exposed sample. Similarly, carvacrol showed significant (p < 0.05) antigenotoxic effect at concentrations of 2.5 μg/mL and 5.0 μg/mL against malathion. We also studied the effect of GSTT1 and GSTM1 on the genotoxicity of malathion and antigenotoxic potential of curcumin and carvacrol. We observed that there is a statistically significant (p < 0.05) reduction in the frequency of SCE in case of curcumin and carvacrol as compared to malathion, but we did not observe any significant relationship (p > 0.05) between GSTT1 and GSTM1 polymorphism and the genotoxicity of malathion and antigenotoxic potential of curcumin and carvacrol.

Induction of cytotoxic and genotoxic responses by natural and novel quercetin glycosides

The flavonoids quercetin, and its natural glycosides isoquercetin and rutin, are phytochemicals commonly consumed in plant-derived foods. Semi-synthetic water-soluble isoquercetin and rutin glycosides, maltooligosyl isoquercetin, monoglucosyl rutin and maltooligosyl rutin were developed by synthetic glycosylation to overcome solubility challenges for improved incorporation in food and medicinal applications. Quercetin and its natural glycosides are known to induce genetic instability and decrease cell proliferation. Using a system of Chinese hamster ovary (CHO) cells, this study examined the differences in cytotoxic and genotoxic responses induced by natural and synthetic flavonoids. Bioactivity evaluations using poly(ADP-ribose) polymerase (PARP) ELISA showed that the synthetic flavonoids were less effective in inhibiting PARP than the natural flavonoids, where PARP inhibitory effects decreased with glycosylation of flavonoids. In the genotoxic studies, treatments with flavonoids at a concentration range of 0.2μM–1mM induced significant frequencies of sister chromatid exchange (SCE) and micronuclei in CHO cells compared to spontaneous occurrences. The synthetic flavonoids monoglucosyl rutin and maltooligosyl rutin induced less genotoxic effects than the natural flavonoids. However, maltooligosyl isoquercetin induced similar responses as isoquercetin and rutin. The growth inhibition studies showed glycosylation dependent cytotoxicity in natural flavonoids. The quercetin aglycone exhibited the highest toxicity out of all the flavonoids studied. Differences in growth inhibition were not observed between the synthetic flavonoids, maltooligosyl isoquercetin and monoglucosyl rutin, and natural isoquercetin and rutin, respectively. Maltooligosyl rutin induced less cytotoxicity than rutin and monoglucosyl rutin. Our in vitro studies demonstrated that the synthetic flavonoids generally induced less genotoxic responses than their natural counterparts.

Olanzapine: evaluation of the in vivo cytogenetic effect.

Olanzapine (OLZ), an atypical antipsychotic, is licensed for use in the treatment of schizophrenia and other psychiatric disorders. OLZ cytogenetic effects were investigated by evaluating the frequency of Sister Chromatid Exchanges (SCEs) and Proliferation Rate Index (PRI) in cultured lymphocytes of schizophrenic patients who were under treatment of OLZ. SCE estimation is one of the most sensitive biomarkers of potential cytotoxicity, while PRI is used as a valuable marker of cytostatic activity. Our results showed a statistically significant increase of SCEs in the cultured lymphocytes of patients (p < 0,001) compared to the lymphocytes of healthy donors, a statistically significant increase of SCEs (p < 0.001) in the lymphocytes of smoker patients compared to those of non-smoker patients and a statistically significant increase of SCEs (p < 0.001) in the lymphocytes of chronic recipients of OLZ compared to those of the patients with recent initiation of treatment. We did not detect any statistically significant differences with respect to PRI between the various groups examined. Our results indicate a mild cytotoxic-but not cytostatic-effect of OLZ which was more prominent in smokers and in chronically treated patients. That effect should be taken into consideration by psychiatrists upon assessing the benefit/risk ratio of their prescriptions.

Deferasirox-induced cytogenetic responses

Deferasirox (commercially formulated as Exjade®) is one of the effective iron chelators used in treatment of iron overload diseases. In this study the effect of this substance for chromosome aberration, sister chromatid exchange and mitotic index was studied by in vitro (by using human peripheral lymphocytes) and in vivo (by using rat) analysis.Deferasirox increased the sister chromatid exchange frequency in all tested concentrations and periods in vitro. Also, in the presence of metabolic activator, the substance led to a statistically significant increase in the sister chromatid exchange frequencies only at high concentration. While in in vitro analysis the substance significantly increased abnormal cell percentages in all concentrations, in in vivo study the substance increased chromosome aberrations only in two concentrations at 12h treatment. In the cultured lymphocytes, deferasirox showed cytotoxicity by significantly reducing proliferation index and mitotic index values. While in the presence of metabolic activation it did not affect the proliferation index frequency, it had a stimulant effect on the mitotic index frequency. Deferasirox reduced significantly the mitotic index value in the bone marrow cells especially in high concentration and short treatment period (12h).

Evaluation of Genomic Damage in Peripheral Lymphocytes from Occupationally Exposed Anesthetists: Assessment of the Effects of Age, Sex, and GSTT1 Gene Polymorphism.

Occupational exposure to anaesthetic gases is one of the major hazards to healthcare personnel. We evaluated the cytogenetic effects of chronic exposure to low concentrations of anaesthetic gases in operating theatres. The study included 21 anesthetists and 21 control subjects who matched in age and gender. Chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) assays were performed. All subjects were also genotyped for glutathione S-transferase T1 (GSTT1) gene polymorphisms. Significant differences were found between exposed and controls in terms of SCEs frequency (P = 0.001) and replication index value (P = 0.005), but not in terms of CAs (P = 0.201) and aberrant cells (P = 0.227) frequencies. Regression analyses indicated that age and the years of employment did not influence the level of chromosomal damage in both groups. Finally, among anesthetists, GSTT1 null individuals showed a significant higher frequency of SCE with respect to GSTT1-positive subjects.

Defective Repair of Uracil Causes Telomere Defects in Mouse Hematopoietic Cells

Uracil in the genome can result from misincorporation of dUTP instead of dTTP during DNA synthesis, and is primarily removed by uracil DNA glycosylase (UNG) during base excision repair. Telomeres contain long arrays of TTAGGG repeats and may be susceptible to uracil misincorporation. Using model telomeric DNA substrates, we showed that the position and number of uracil substitutions of thymine in telomeric DNA decreased recognition by the telomere single-strand binding protein, POT1. In primary mouse hematopoietic cells, uracil was detectable at telomeres, and UNG deficiency further increased uracil loads and led to abnormal telomere lengthening. In UNG-deficient cells, the frequencies of sister chromatid exchange and fragility in telomeres also significantly increased in the absence of telomerase. Thus, accumulation of uracil and/or UNG deficiency interferes with telomere maintenance, thereby underscoring the necessity of UNG-initiated base excision repair for the preservation of telomere integrity.

Erratum to: “Antagonistic effects of Satureja hortensis essential oil against AFB1, on human lymphocytes in vitro”

Satureja hortensis L. (Lamiaceae) has been used as a folk remedy to treat various such as cramps, muscle pains, nausea, indigestion, diarrhea, and infectious diseases. In this study, the antagonistic effects of essential oil of S. hortensis (SHE) were studied against aflatoxin B1 (AFB1) in human lymphocytes in vitro. The analysis of the essential oil was performed by using Gas chromatography-mass spectrometry (GC-MS). Anti-genotoxic effects of the SHEs was evaluated using sister chromatid exchange (SCE), micronuclei (MN) tests against AFB1. Also level of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities used to determine the anti-oxidative effects of the SHEs. This result showed AFB1 (5 microM) increased the frequencies of SCE, MN and the level of MDA. AFB1 at the same concentration decreased the activities of SOD and GPx. However, different concentrations of SHE with AFB1 decreased the frequency of SCE and MN and level of MDA and also increased the activities of SOD and GPx significantly. Especially, the 1.0, 1.5, 2.0 microL dose of SHE are more effective than other doses. The results of this experiment have clearly shown that SHE has strong antioxidative and antigenotoxic effects, these biological activities of SHEs can be due to its component.

Genotoxic and Cytotoxic Damage by Cyclophosphamide and Adriamycin as a Response to Treatment in Breast Cancer Patients: Pilot Study

The aim of this study was to evaluate the genotoxicity induced by cyclophosphamide-adriamycin treatment in breast cancer patients through the frequencies of Sister Chromatid Exchange (SCE), Replication Index (RI), Mitotic Index (MI) and Cell Proliferation Index (CPI) and to study the possible association between biomarkers of genotoxicity and the early response to treatment. The frequencies were obtained before and immediately after therapy from 17 patients with breast cancer (p

Enhancement of Sister Chromatid Exchanges (SCEs) in Peripheral Blood Lymphocytes of Women with Polycystic Ovary Syndrome (PCOS) &amp;lt;i&amp;gt;in Vitro&amp;lt;/i&amp;gt;

The aim of the present study was to determine the level of underlying DNA damage in females with PCOS. Twenty-two women with PCOS and twenty-two healthy controls were included in this study. Patients were further categorized into three phenotypic subgroups: Subgroup A, oligo/anovulation (ANOV) and polycystic ovaries (PCO); Subgroup B, hyperandrogenism (HA) as a main characteristic (HA + ANOV or HA + PCO); Subgroup C, all three conditions present (HA + ANOV + PCO). The frequency of sister chromatid exchanges (SCEs) was used as an index of cytogenetic damage. Proliferation rate index (PRI), mitotic index (MI), average generation time (AGT) and population doubling time (PDT) were also evaluated. A significant (p < 0.01) increase in SCE levels along with a significant (p < 0.01) reduction in PRIs and MIs were observed in women with PCOS compared with healthy subjects. Additionally, subgroup C demonstrated statistically significant differences compared with others, while subgroup A had similar results with healthy females. Our results suggest that females with PCOS show increased chromosomal instability in peripheral lymphocytes and a consequent inability of the cells to promote their own mitotic cycle. A positive correlation between DNA damage and PCOS phenotypes is also reported.

Evaluation of Possible Genotoxic Activity of Dirithromycin in Cultured Human Lymphocytes.

Dirithromycin antibiotic is a 14-membered lactone ring macrolide and is widely used in medicine to treat many different types of bacterial infections. In the present study, the possible genotoxicity of dirithromycin was evaluated in cultured human lymphocytes by using sister chromatid exchanges (SCEs), chromosome aberration (CA), and micronucleus (MN) tests and also cell proliferation kinetics such as mitotic index (MI), replication index (RI), and nuclear division index (NDI) were analyzed for cytotoxicity. Cell cultures were treated with four different concentrations of dirithromycin (37.75, 67.50, 125, and 250 µg/mL) for 24 and 48 h periods. Dirithromycin significantly induced SCE and MN frequency at all concentrations in both 24 and 48 h treated cells. In addition, CA level has been markedly increased in the cells treated with almost all concentrations of dirithromycin for 24 (except 37.75 µg/mL) and 48 h treatment periods as compared to control. However, MI, RI, and NDI values were not affected by the dirithromycin treatment (p > 0.05). The results of this study indicated that dirithromycin treatment caused genetic damage by increasing the level of cytogenetic endpoints, suggesting its genotoxic and mutagenic action on human lymphocytes in vitro.

Biomarkers of genotoxicity measured in human lymphocytes exposed to benzo[a]pyrene: Aneugenic effect, and involvement multiple primary DNA lesions

Benzo-a-pyrene (B[a]P) is a polycyclic aromatic hydrocarbon classified as carcinogenic to human. Its metabolic activation leads to production of metabolites forming adducts with DNA, being at origin of B[a]P-induced DNA damages, mutagenesis and carcinogenesis. Human blood lymphocytes cultures established from 25 subjects aged 20 to 30 years old, living in Montreal (Quebec, Canada) were exposed to B[a]P (0.4, 4, 20 and 40 µM) for 24 h, then washed and cultivated without B[a]P for an additional 24 h. B[a]P-DNA adducts, DNA single-strand breaks (SSBs), sister chromatid exchanges (SCEs), chromosomal aberrations (CAs) and micronuclei (MN) were analysed. Fluorescent in situ hybridization (FISH) analysis of MN using a pancentromeric probe was also done to assess MN content. Significantly increased formation of B[a]P-DNA adducts, CAs, MN and SCEs were observed starting at [B[a]P]=0.4 µM (p<0.01), with a significant decrease of B[a]P-DNA adducts and MN after exposure to 20 µM B[a]P. For DNA SSBs, no significant increase was observed in all conditions. Besides, FISH analysis showed that B[a]P-induced MN mostly contain centromeres (77.1% vs 68.5% for the control, p<0.01), and specifically three or more centromeres (p<0.01). This study suggests an aneugenic effect of B[a]P in human lymphocytes. Finally, statistical analysis by multiple linear regression showed that two variables (B[a]P exposure level and B[a]P-DNA adducts) significantly explained 53% of observed variability in SCE test, while the percentage of cell presenting a high frequency of SCE (% HFC) was the only variable significantly explaining the observed variability in CA and MN test (34% and 12%, respectively). These observations indicate that DNA breaks, in addition to B[a]P-DNA adducts, contributed to SCEs formation.

Increased sister chromatid exchange in peripheral blood lymphocytes from humans exposed to pesticide: evidence based on a meta-analysis.

Sister chromatid exchange (SCE) in human peripheral blood lymphocytes is one of the most extensively studied biomarkers employed to evaluate genetic damage subsequent to pesticide exposure. To estimate the pooled levels of SCE in human peripheral blood lymphocytes among population exposed to pesticide. Meta-analysis on the association between SCE frequency and pesticide exposure was performed with STATA 10.0 software package and Review Manager 5.0.24 in this study. The overall means of SCE were 7.88 [95% confidence intervals (95%CI): 6.71-9.04] for exposure group and 6.05 (95%CI: 5.13-6.95) for controls, respectively. There was statistically significant difference in the SCE frequency in human peripheral blood lymphocytes between pesticide-exposed groups and control groups, and the summary estimate of weighted mean difference was 1.69 (95%CI: 1.01-2.38). We also observed that pesticide-exposed population had significantly higher SCE frequency than control groups among smokers, nonsmokers, pesticide applicator, pesticide producer, other exposure population and Asian population in stratified analyses. Data indicate that the SCE frequency in human peripheral blood lymphocytes might be an indicator of early genetic effects for pesticide-exposed populations.

Sister chromatid exchange: A possible approach to characterize familial breast cancer patients.

Sister chromatid exchange (SCE) frequency is widely used as an indicator of spontaneous chromosome instability. We investigated SCE frequency in the peripheral blood lymphocytes of familial and sporadic breast cancer (BC) patients from the Apulian Caucasian Population. Eighty-one patients were enrolled: 22 with familial history and 59 sporadic patients. Eleven familial patients had an 'increased risk' of BRCA gene mutation (BRCAPro ≥ 10%) and were candidates for BRCA1 and BRCA2 mutation analysis. For these reasons, we stratified the 22 familial BC patients in two group: 'low-risk' (n=11) and 'high-risk' (n=11) patients for BRCA gene mutations. Two of these 11 'high-risk' patients (18%) had pathogenic mutations in the BRCA2 gene. The subjects were not cigarette smokers or alcohol or drug users, and had no genetic disorders or chronic diseases affecting the family. Our results showed a significant increase in SCE frequency in the familial (5.305 ± 1.088/metaphase) (P<0.0001) and the sporadic patients (3.943 ± 0.552) (P<0.0001) compared to the controls (3.197 ± 0.649). We found that the SCE frequency was always significantly higher in familial than in sporadic patients, regardless of their clinicopathological characteristics. Moreover, we observed that the frequency of SCE in BRCA2 mutation carrier patients was higher compared to patients without mutations in BRCA1/2 genes. These findings highlight an intrinsic genomic instability in familial patients, and we suggest that SCE frequency may be used as a biomarker to better characterize familial BC.