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1.
Environ Monit Assess ; 193(5): 243, 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33821353

RESUMEN

The aim of this study was to assess the genotoxic effects of sediment elutriates of an aquatic ecosystem. Sediment samples were taken from Limache stream, located in central Chile. The tests were carried out on sediment elutriates. Genotoxicity was determined by bioassay with Allium cepa. The percentage of germination, root growth, mitotic index, and frequency of chromosome aberrations were determined. The results show a significant increase in chromosome aberrations and decrease of the mitotic index in Allium cepa in all the sediment elutriates compared to the control. No significant differences were observed in the percentages of germination or root growth among the sediment elutriates. A negative correlation was found between the mitotic index and chromosomal aberrations. In conclusion, genotoxic variables are more sensitive than growth variables. The sediments contain chemical agents in bioavailable concentrations that produce genotoxic effects. Allium cepa test proved to be a sensitive indicator of genotoxic contaminants in sediment elutriates of the Limache stream in central Chile.


Asunto(s)
Allium , Cebollas , Chile , Aberraciones Cromosómicas , Daño del ADN , Ecosistema , Monitoreo del Ambiente , Humanos , Índice Mitótico , Raíces de Plantas , Ríos
2.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(2): 319-325, 2021 Mar.
Artículo en Chino | MEDLINE | ID: mdl-33829709

RESUMEN

Objective: To explore the application of array-based comparative genomic hybridization (a-CGH) technology in the prenatal diagnostic assessment of abnormal serological prenatal screening results of Down's syndrome (DS). Methods: A total of 3 578 amniotic fluid samples from pregnant women who underwent amniocentesis for prenatal diagnosis solely due to abnormal serological prenatal screening results were selected. The samples were categorized into 3 groups, 2 624 in the high-risk group, 662 in the borderline-risk group, and 292 in the abnormal multiple of median (MoM) group. a-CGH was performed on the Agilent CGX ™ (8×60K) platform and the data were analyzed by the Genoglyphix ® software. Results: The overall detection rate of chromosomal abnormalities was 3.38% (121/3 578). Among the chromosomal abnormalities, 49.59% (60/121) was aneuploidies, 42.15% (51/121) was pathogenic copy number variants (pCNVs), and 8.26% (10/121) was likely pathogenic CNVs (lpCNVs). The detection rate of copy number variant of uncertain significance (VUS) was 1.03% (37/3 578). In the high-risk, the borderline-risk and the abnormal MoM groups, the detection rate of chromosomal abnormalities was 3.54% (93/2 624), 2.87% (19/662) and 3.08% (9/292), respectively; the detection rate of p/lp CNVs was 1.64% (43/2 624), 1.81% (12/662) and 2.05% (6/292), respectively; the detection rate of trisomy 21 and trisomy 18 was 1.37% (36/2 624), 0.76% (5/662) and 0.34% (1/292) in the three groups, respectively. There were no significant differences in all the detection rate among these groups ( P>0.05). One sample with X(51)/XYY(49) confirmed by fluorescence in situ hybridization (FISH) was misdiagnosed by a-CGH. Conclusion: Prenatal diagnosis with a-CGH is of great significance for reducing birth defects in pregnancies with abnormal serological prenatal screening results of DS. It can also be used to detect CNVs of microdeletion/microduplication syndromes.


Asunto(s)
Síndrome de Down , Aberraciones Cromosómicas , Hibridación Genómica Comparativa , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Femenino , Humanos , Hibridación Fluorescente in Situ , Embarazo , Diagnóstico Prenatal
3.
BMC Bioinformatics ; 22(1): 100, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33648439

RESUMEN

BACKGROUND: There have been many recent breakthroughs in processing and analyzing large-scale data sets in biomedical informatics. For example, the CytoGPS algorithm has enabled the use of text-based karyotypes by transforming them into a binary model. However, such advances are accompanied by new problems of data sparsity, heterogeneity, and noisiness that are magnified by the large-scale multidimensional nature of the data. To address these problems, we developed the Mercator R package, which processes and visualizes binary biomedical data. We use Mercator to address biomedical questions of cytogenetic patterns relating to lymphoid hematologic malignancies, which include a broad set of leukemias and lymphomas. Karyotype data are one of the most common form of genetic data collected on lymphoid malignancies, because karyotyping is part of the standard of care in these cancers. RESULTS: In this paper we combine the analytic power of CytoGPS and Mercator to perform a large-scale multidimensional pattern recognition study on 22,741 karyotype samples in 47 different hematologic malignancies obtained from the public Mitelman database. CONCLUSION: Our findings indicate that Mercator was able to identify both known and novel cytogenetic patterns across different lymphoid malignancies, furthering our understanding of the genetics of these diseases.


Asunto(s)
Enfermedades Hematológicas , Cariotipificación , Neoplasias , Aberraciones Cromosómicas , Humanos , Cariotipo
4.
Ann Hematol ; 100(5): 1251-1260, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33686491

RESUMEN

The prognostic value of chromosomal 1q21 gain in newly diagnosed multiple myeloma (NDMM) remains controversial. Add-on Myc aberrations may further worsen the outcome. To investigate whether specific genes located at the 1q21 region, such as myeloid cell leukemia 1 (Mcl-1), are involved in NDMM progression, we examined bone marrow cytogenetic abnormalities in 153 patients with NDMM by fluorescence in situ hybridization. Their response to treatment and survival was also analyzed. C-Myc and Mcl-1 expressions in bone marrow samples were analyzed by RT-PCR. The expression of Mcl-1 was evaluated in bone marrow sections by immunohistochemistry. MM cell lines were transfected with Mcl-1 siRNA. 1q21 gain was present in 55/153 (35.9%) patients and strongly associated with Myc rearrangement (31/153, 20.3%, P = 0.004). A positive correlation was observed between Myc and Mcl-1 mRNA levels in bone marrow cells from 47 patients (r = 0.57, P < 0.001). The combination of 1q21 gain and Myc rearrangement was associated with poorer overall survival than Myc rearrangement alone (16.8 vs. 27.9 months, P = 0.077) or 1q21 gain alone (16.8 vs. 60.7 months, P < 0.01). High Mcl-1 protein expression in bone marrow plasma cells was associated with Myc rearrangement. Mcl-1 silencing by siRNA inhibited Myc protein expression in three myeloma cell lines. Treatment with the small-molecule Mcl-1 inhibitor, UMI-77, produced similar results. Overall, the combination of Myc rearrangement and 1q21 gain was associated with particularly poor prognosis in patients with MM. Furthermore, our data are consistent with Mcl-1-dependent Myc protein activation.


Asunto(s)
Mieloma Múltiple/genética , Proteínas Proto-Oncogénicas c-myc/genética , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Aberraciones Cromosómicas , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/patología , Pronóstico , ARN Mensajero/genética
5.
Mutat Res ; 863-864: 503312, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33678244

RESUMEN

Most blood components for transfusions are irradiated ex vivo to prevent transfusion-associated graft-versus-host disease (TA-GvHD); this irradiation can potentially affect the cytogenetic dose assessment of patients showing acute radiation syndrome (ARS) with bone marrow suppression or acute anaemia. Whole blood samples from five donors were irradiated with 0, 10 or 25 Gy γ-rays. The mitotic activity of each cultured blood sample was measured by calculating the mitotic index. A dicentric chromosome assay was used to evaluate the chromosomal aberrations and absorbed dose of blood lymphocytes. Mitogenic activity and scorable metaphase spreads were significantly decreased in the blood samples irradiated with 10 and 25 Gy (p < 0.001). Moreover, a significant increase in the mean scores of all types of chromosomal aberrations in the 10 Gy γ-irradiated samples was observed, with the estimated dose being 11.3 Gy (95% CI: 10.67-11.95 Gy); however, we were unable to estimate the exposure dose in the 25 Gy γ-irradiated samples due to a limited number of scorable metaphase spreads. The mitotic index of the 25 Gy γ-irradiated whole blood samples was significantly suppressed by more than 4-log fold. Thus, in the present study, we evaluated the effects of recommended radiation doses in γ-irradiated transplantation blood components using cytogenetic dosimetry. These results suggest that the partial transfusion of blood components to patients with ARS or acute anaemia did not compromise the estimation of the exposure dose using cytogenetic dosimetry.


Asunto(s)
Aberraciones Cromosómicas/efectos de la radiación , Rayos gamma/efectos adversos , Linfocitos/metabolismo , Adulto , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Linfocitos/patología , Masculino , Dosis de Radiación
6.
Mutat Res ; 863-864: 503313, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33678245

RESUMEN

Biological dosimetry of ionizing radiation (IR) exposure relies on validated cytogenetic tests measuring the frequencies of micronuclei (MN) and dicentric chromosomes (DC). IR also causes oxidative damage of biomolecules, including DNA. We evaluated IR-induced genotoxic and oxidative damage in a carefully defined cohort of healthy donors, reducing confounding factors as much as possible. Frequencies of MN and DC (peripheral blood lymphocyte cultures) and oxidative stress parameters (plasma) were quantified. We observed dose dependence of both cytogenetic and biochemical endpoints, independent of age, sex, and smoking habits. Oxidative stress parameters, especially oxidative stress index, malondialdehyde, advanced oxidation protein products, and catalase, may be used confidently to assess IR-induced damage, if cytogenetic results are unavailable.


Asunto(s)
Aberraciones Cromosómicas/efectos de la radiación , Linfocitos/metabolismo , Estrés Oxidativo/efectos de la radiación , Plasma/metabolismo , Traumatismos por Radiación/metabolismo , Radiación Ionizante , Adulto , Femenino , Humanos , Linfocitos/patología , Masculino , Persona de Mediana Edad , Traumatismos por Radiación/patología
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(3): 210-213, 2021 Mar 10.
Artículo en Chino | MEDLINE | ID: mdl-33751526

RESUMEN

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for fetal duodenal obstruction (DO). METHODS: Fifty-one fetuses with DO identified by prenatal ultrasound were divided into DO only group and DO with other anomaly group. CMA was carried out on amniotic fluid or umbilical blood samples, and the outcome of pregnancy of all cases were followed up. RESULTS: Eight fetuses (15.7%) were found with genomic abnormalities, which included 3 chromosomal aneuploidies and 5 copy number variations (CNVs), including one 17q12 microduplication syndrome, one 13q21.33q31.1 microdeletion, one 13q21.32q22.3 deletion, one 13q21.2q31.1 deletion and one 1q43q44 duplication. EDNRB from 13q and HNF1B from 17q12 are candidate genes for fetal DO. No significant difference was found in the detection rate of pathogenic CNVs between the DO only and DO with other anomaly groups (9.5% vs.11.1%, P> 0.05). There were 39 live borns, 1 stillbirth, and 11 artificial abortions (8 with abnormal CMA results). CONCLUSION: There is a correlation between fetal DO and abnormal copy number of the genome, for which prenatal diagnosis is necessary. CMA not only can detect microdeletions/microduplications, but also identify pathogenic genes, which can facilitate prenatal diagnosis, genetic counseling and prognosis for the fetus.


Asunto(s)
Aberraciones Cromosómicas , Variaciones en el Número de Copia de ADN , Obstrucción Duodenal , Obstrucción Duodenal/genética , Femenino , Feto , Humanos , Análisis por Micromatrices , Embarazo , Diagnóstico Prenatal
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(3): 228-231, 2021 Mar 10.
Artículo en Chino | MEDLINE | ID: mdl-33751530

RESUMEN

OBJECTIVE: To assess the value of copy number variations (CNVs) and chromosomal karyotyping analysis for patients with intellectual disability/developmental delay (ID/DD). METHODS: Chromosomal karyotype analysis was applied to 530 children diagnosed with ID/DD. Single nucleotide polymorphism array (SNP-array) was further applied for 120 children with unknown etiology. RESULTS: Among the 530 children with ID/DD, 104 (19.62%) were detected with chromosomal abnormalities. For the 120 children analyzed by SNP-array, 44 (36.67%) were detected with CNVs, among which 20 were predicted as pathogenic, 6 as likely pathogenic, 10 as variants of unknown significance, 7 as likely benign,and 1 as loss of heterozygosity. CONCLUSION: SNP-array can facilitate delineation of the etiology of patients with ID/DD, which may provide a basis for their prognosis, consultation and clinical intervention.


Asunto(s)
Variaciones en el Número de Copia de ADN , Discapacidades del Desarrollo , Discapacidad Intelectual , Niño , Aberraciones Cromosómicas , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/genética , Humanos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Cariotipificación
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(3): 268-270, 2021 Mar 10.
Artículo en Chino | MEDLINE | ID: mdl-33751539

RESUMEN

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the prenatal diagnosis of a fetus with structural anomaly detected by ultrasonography. METHODS: The fetus and its parents were subjected to chromosomal karyotyping and CMA analysis. RESULTS: The fetus was found to carry a 46,XN,t(8;11)(q21.2;q13) translocation which was inherited from its mother. CMA has found no copy number variations (CNVs) in both parents but a de novo 2.00 Mb microdeletion in the fetus at 8q13.3. CONCLUSION: CMA is capable of detecting microdeletions and microduplications in fetuses with translocations detected by karyotyping analysis.


Asunto(s)
Aberraciones Cromosómicas , Diagnóstico Prenatal , Deleción Cromosómica , Cromosomas Humanos Par 8 , Variaciones en el Número de Copia de ADN , Femenino , Feto , Humanos , Cariotipificación , Análisis por Micromatrices , Embarazo
10.
Medicine (Baltimore) ; 100(12): e25277, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33761731

RESUMEN

ABSTRACT: Drug-resistant epilepsy (DRE) affects 7% to 20% of children with epilepsy. Although some risk factors for DRE have been identified, the results have not been consistent. Moreover, data regarding the risk factors for epilepsy and its seizure outcome in the first 2 years of life are limited.We analyzed data for children aged 0 to 2 years with epilepsy and neurodevelopmental disability from January, 2013, through December, 2017. These patients were followed up to compare the risk of DRE in patients with genetic defect (genetic group) with that without genetic defect (nongenetic group). Additionally, we conducted a meta-analysis to identify the pooled prevalence of genetic factors in children with DRE.A total of 96 patients were enrolled. A total of 68 patients were enrolled in the nongenetic group, whereas 28 patients were enrolled in the genetic group. The overall DRE risk in the genetic group was 6.5 times (95% confidence interval [CI], 2.15-19.6; p = 0.03) higher than that in the nongenetic group. Separately, a total of 1308 DRE patients were participated in the meta-analysis. The pooled prevalence of these patients with genetic factors was 22.8% (95% CI 17.4-29.3).The genetic defect plays a crucial role in the development of DRE in younger children with epilepsy and neurodevelopmental disability. The results can serve as a reference for further studies of epilepsy panel design and may also assist in the development of improved treatments and prevention strategies for DRE.


Asunto(s)
Aberraciones Cromosómicas/estadística & datos numéricos , Discapacidades del Desarrollo , Epilepsia Refractaria , Enfermedades Genéticas Congénitas , Medición de Riesgo/métodos , China/epidemiología , Correlación de Datos , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/epidemiología , Epilepsia Refractaria/diagnóstico , Epilepsia Refractaria/epidemiología , Epilepsia Refractaria/genética , Femenino , Enfermedades Genéticas Congénitas/diagnóstico , Enfermedades Genéticas Congénitas/epidemiología , Humanos , Lactante , Recién Nacido , Masculino , Mutación , Canal de Sodio Activado por Voltaje NAV1.1/genética , Canal de Sodio Activado por Voltaje NAV1.6/genética , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Proteína 2 del Complejo de la Esclerosis Tuberosa/genética
11.
Int J Mol Sci ; 22(4)2021 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-33671467

RESUMEN

Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder related to the lack of a functional paternal copy of chromosome 15q11-q13. Several clinical manifestations are reported, such as short stature, cognitive and behavioral disability, temperature instability, hypotonia, hypersomnia, hyperphagia, and multiple endocrine abnormalities, including growth hormone deficiency and hypogonadism. The hypogonadism in PWS is due to central and peripheral mechanisms involving the hypothalamus-pituitary-gonadal axis. The early diagnosis and management of hypogonadism in PWS are both important for physicians in order to reach a better quality of life for these patients. The aim of this study is to summarize and investigate causes and possible therapies for hypogonadism in PWS. Additional studies are further needed to clarify the role of different genes related to hypogonadism and to establish a common and evidence-based therapy.


Asunto(s)
Hipogonadismo/complicaciones , Síndrome de Prader-Willi/complicaciones , Aberraciones Cromosómicas , Hormonas/metabolismo , Humanos , Hipogonadismo/fisiopatología , Hipogonadismo/terapia , Síndrome de Prader-Willi/epidemiología , Síndrome de Prader-Willi/genética
12.
Int J Mol Sci ; 22(5)2021 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-33673497

RESUMEN

Both cell and animal studies have shown that complete or partial deficiency of methionine inhibits tumor growth. Consequently, the potential implementation of this nutritional intervention has recently been of great interest for the treatment of cancer patients. Unfortunately, diet alteration can also affect healthy immune cells such as monocytes/macrophages and their precursor cells in bone marrow. As around half of cancer patients are treated with radiotherapy, the potential deleterious effect of dietary methionine deficiency on immune cells prior to and/or following irradiation needs to be evaluated. Therefore, we examined whether modulation of methionine content alters genetic stability in the murine RAW 264.7 monocyte/macrophage cell line in vitro by chromosomal analysis after 1-month culture in a methionine-deficient or supplemented medium. We also analyzed chromosomal aberrations in the bone marrow cells of CBA/J mice fed with methionine-deficient or supplemented diet for 2 months. While all RAW 264.7 cells revealed a complex translocation involving three chromosomes, three different clones based on the banding pattern of chromosome 9 were identified. Methionine deficiency altered the ratio of the three clones and increased chromosomal aberrations and DNA damage in RAW 264.7. Methionine deficiency also increased radiation-induced chromosomal aberration and DNA damage in RAW 264.7 cells. Furthermore, mice maintained on a methionine-deficient diet showed more chromosomal aberrations in bone marrow cells than those given methionine-adequate or supplemented diets. These findings suggest that caution is warranted for clinical implementation of methionine-deficient diet concurrent with conventional cancer therapy.


Asunto(s)
Células de la Médula Ósea/metabolismo , Aberraciones Cromosómicas , Daño del ADN , Desnutrición/genética , Metionina/deficiencia , Animales , Reparación del ADN , Dieta , Macrófagos , Masculino , Desnutrición/metabolismo , Ratones , Ratones Endogámicos CBA , Monocitos , Células RAW 264.7
13.
Int J Mol Sci ; 22(4)2021 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-33562221

RESUMEN

The 15q11.2 BP1-BP2 deletion (Burnside-Butler) syndrome is emerging as the most common cytogenetic finding in patients with neurodevelopmental or autism spectrum disorders (ASD) presenting for microarray genetic testing. Clinical findings in Burnside-Butler syndrome include developmental and motor delays, congenital abnormalities, learning and behavioral problems, and abnormal brain findings. To better define symptom presentation, we performed comprehensive cognitive and behavioral testing, collected medical and family histories, and conducted clinical genetic evaluations. The 15q11.2 BP1-BP2 region includes the TUBGCP5, CYFIP1, NIPA1, and NIPA2 genes. To determine if additional genomic variation outside of the 15q11.2 region influences expression of symptoms in Burnside-Butler syndrome, whole-exome sequencing was performed on the parents and affected children for the first time in five families with at least one parent and child with the 15q1l.2 BP1-BP2 deletion. In total, there were 453 genes with possibly damaging variants identified across all of the affected children. Of these, 99 genes had exclusively de novo variants and 107 had variants inherited exclusively from the parent without the deletion. There were three genes (APBB1, GOLGA2, and MEOX1) with de novo variants that encode proteins evidenced to interact with CYFIP1. In addition, one other gene of interest (FAT3) had variants inherited from the parent without the deletion and encoded a protein interacting with CYFIP1. The affected individuals commonly displayed a neurodevelopmental phenotype including ASD, speech delay, abnormal reflexes, and coordination issues along with craniofacial findings and orthopedic-related connective tissue problems. Of the 453 genes with variants, 35 were associated with ASD. On average, each affected child had variants in 6 distinct ASD-associated genes (x¯ = 6.33, sd = 3.01). In addition, 32 genes with variants were included on clinical testing panels from Clinical Laboratory Improvement Amendments (CLIA) approved and accredited commercial laboratories reflecting other observed phenotypes. Notably, the dataset analyzed in this study was small and reported results will require validation in larger samples as well as functional follow-up. Regardless, we anticipate that results from our study will inform future research into the genetic factors influencing diverse symptoms in patients with Burnside-Butler syndrome, an emerging disorder with a neurodevelopmental behavioral phenotype.


Asunto(s)
Cromosomas Humanos Par 15/genética , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Discapacidad Intelectual/genética , Discapacidad Intelectual/psicología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Aberraciones Cromosómicas , Cognición , Familia , Femenino , Humanos , Discapacidad Intelectual/patología , Masculino , Persona de Mediana Edad , Equilibrio Postural , Secuenciación del Exoma Completo , Adulto Joven
14.
Mutat Res ; 861-862: 503275, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33551094

RESUMEN

Chromosome aberrations in the peripheral blood lymphocytes of styrene exposed workers have been suggested as a potential early marker for cancer risk. We performed a critical review and abstracted data from all studies using current chromosome aberration scoring criteria and providing at least a mean and standard deviation or standard error for the exposed and comparison groups. Using these data, we conducted a meta-analysis of occupational styrene exposed workers and incidence of chromosome aberrations. Our meta-analysis used the standardized mean difference as the summary statistic since all studies assess the same outcome but use different comparison populations. The primary meta-analysis of the 20 comparisons of 505 styrene exposed workers to 532 comparison workers found a meta-mean difference of 0.361 (95 % CI -0.084 to 0.807, random effects model), but there was substantial lack of consistency across studies (I2 of 90.11, p-value <0.001, fixed effect model). Studies with higher styrene exposures had lower mean standard differences compared to studies with lower styrene exposures. While studies of styrene workers overall had a slight increase in chromosomal aberrations relative to comparison groups, the lack of consistency across studies and the absence of an exposure response and other limitations of the reviewed studies including inadequate exposure assessment, small numbers of participants per study, and poorly matched exposed and comparison workers, we find insufficient evidence to support a conclusion that styrene exposure increases chromosome aberration frequencies in styrene workers.


Asunto(s)
Aberraciones Cromosómicas , Enfermedades Profesionales/epidemiología , Exposición Profesional/efectos adversos , Estireno/efectos adversos , Humanos , Incidencia , Enfermedades Profesionales/inducido químicamente , Estados Unidos/epidemiología
15.
Mutat Res ; 861-862: 503276, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33551095

RESUMEN

A radiation accident occurred in Bursa, Turkey, in July 2005. An industrial radiographer was exposed to industrial iridium-192 gamma rays for 5 h while laying the natural gas line. After 5 h, the victim had a break because of vomiting and nausea. He ended his work, considering that he might have been exposed to radiation. In a few days, erythema, pain, desquamation, edema started in both hands of the victim. The biological dose assessment was started based on frequencies of dicentrics and rings in peripheral blood lymphocytes ten days after the radiation accident. 6 repeated blood samples were taken for 9 years and analyzed staining after giemsa. After 9 years, decline at dicentric frequencies is significant, but still, dicentric contain cells were detected, which were a strong indicator for external radiation exposure.


Asunto(s)
Aberraciones Cromosómicas/efectos de la radiación , Análisis Citogenético/métodos , Rayos gamma/efectos adversos , Linfocitos/patología , Exposición a la Radiación/efectos adversos , Liberación de Radiactividad Peligrosa/estadística & datos numéricos , Adulto , Estudios de Seguimiento , Humanos , Linfocitos/efectos de la radiación , Masculino , Turquia
16.
Mutat Res ; 861-862: 503295, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33551098

RESUMEN

Five occupational workers in an industrial sterilization unit at Stamboliyski in Bulgaria were accidentally exposed to a very high specific activity of Cobalt-60 source on June 14, 2011. Initial cytogenetic analysis performed on days 2 and 7 after radiation exposure revealed the whole body absorbed radiation doses of 5.32 Gy for patient 1, 3.40 Gy for patient 2, 2.50 Gy for patient 3, 1.91 Gy for patient 4 and 1.24 Gy for patient 5 [1]. Here, a retrospective multicolor FISH analysis was performed on three patients (patients 1, 2 and 3) using the blood samples collected over a period of 4 years from 2012 through 2015. In all the three patients, cells with stable chromosome aberrations (simple and complex chromosome translocations) were 3-4 folds more than cells with unstable chromosome aberrations (dicentric, rings and excess acentric chromosome fragments). In corroboration with the results reported in the literature, we observed that the time dependent decline of dicentrics, rings and excess acentric fragments occurred much more rapidly than chromosome translocations in the blood samples of the three victims. Further, inter-individual variation in the decline of radiation induced chromosome aberrations was also noticed among the three victims. The reason for the increased persistence of balanced chromosome translocations is not entirely clear but may be attributed to certain subsets of long-lived T-lymphocytes. The retrospective cytogenetic follow up studies on radiation-exposed victims may be useful for determining the extent of genomic/chromosomal instability in the hematopoietic system.


Asunto(s)
Aberraciones Cromosómicas/efectos de la radiación , Análisis Citogenético/métodos , Rayos gamma/efectos adversos , Linfocitos/patología , Exposición a la Radiación/efectos adversos , Liberación de Radiactividad Peligrosa/estadística & datos numéricos , Adulto , Anciano , Femenino , Humanos , Linfocitos/efectos de la radiación , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
17.
Mutat Res ; 861-862: 503306, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33551100

RESUMEN

Inhibiting inflammatory processes or eliminating inflammation represents a logical role in the suppression and treatment strategy of cancer. Several studies have shown that anti-inflammatory drugs (NSAIDs) act as anticancer agents while reducing metastases and mortality rate. NSAIDs are seriously limited by their side effects and toxicity, which can become cumulative with their long-term administration for chemoprevention. In the current ex vivo / in vitro study, the genotoxicity mechanisms of NSAIDS in bulk and nanoparticle forms allowed a strategy to prevent and minimise the damage in human lymphocytes. When compared to their bulk forms, acetylsalicylic acid (Aspirin) nano and ibuprofen nano (IBU N), both NSAIDs in 500 µg/mL concentration significantly decreased DNA damage measured by alkaline comet assay. Micronuclei (MNi) frequency also decreased after ASP N (500 µg/mL), ASP B (500 µg/mL) and IBU N (200 µg/mL) in prostate cancer patients and healthy individuals, however, the ibuprofen bulk (200 µg/mL) showed a significant increase in MNi formation in lymphocytes from healthy and prostate cancer patients when compared to the respective untreated lymphocytes. These findings suggest that a reduction in particle size had an impact on the reactivity of the drug, further emphasising the potential of nanoparticles to improve the current treatment options.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Aspirina/farmacología , Aberraciones Cromosómicas/efectos de los fármacos , Daño del ADN , Ibuprofeno/farmacología , Linfocitos/patología , Neoplasias de la Próstata/patología , Anciano , Estudios de Casos y Controles , Humanos , Técnicas In Vitro , Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Nanopartículas , Neoplasias de la Próstata/tratamiento farmacológico
18.
Mutat Res ; 861-862: 503301, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33551102

RESUMEN

Ataxia-telangiectasia (AT) is a rare inherited recessive disorder which is caused by a mutated Ataxia-telangiectasia mutated (ATM) gene. Hallmarks include chromosomal instability, cancer predisposition and increased sensitivity to ionizing radiation. The ATM protein plays an important role in signaling of DNA double-strand breaks (DSB), thereby phosphorylating the histone H2A.X. Non-functional ATM protein leads to defects in DNA damage response, unresolved DSBs and genomic instability. The aim of this study was to evaluate chromosomal aberrations and γH2A.X foci as potential radiation sensitivity biomarkers in AT patients. For this purpose, lymphocytes of 8 AT patients and 10 healthy controls were irradiated and induced DNA damage and DNA repair capacity were detected by the accumulation of γH2A.X foci. The results were heterogeneous among AT patients. Evaluation revealed 2 AT patients with similar γH2A.X foci numbers as controls after 1 h while 3 patients showed a lower induction. In regard to DNA repair, 3 of 5 AT patients showed poor damage repair. Therefore, DNA damage induction and DNA repair as detected by H2A.X phosphorylation revealed individual differences, seems to depend on the underlying individual mutation and thus appears not well suited as a biomarker for radiation sensitivity. In addition, chromosomal aberrations were analyzed by mFISH. An increased frequency of spontaneous chromosomal breakage was characteristic for AT cells. After irradiation, significantly increased rates for non-exchange aberrations, translocations, complex aberrations and dicentric chromosomes were observed in AT patients compared to controls. The results of this study suggested, that complex aberrations and dicentric chromosomes might be a reliable biomarker for radiation sensitivity in AT patients, while non-exchange aberrations and translocations identified both, spontaneous and radiation-induced chromosomal instability.


Asunto(s)
Ataxia Telangiectasia/genética , Aberraciones Cromosómicas , Histonas/genética , Tolerancia a Radiación , Adolescente , Adulto , Ataxia Telangiectasia/patología , Ataxia Telangiectasia/radioterapia , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Estudios de Casos y Controles , Niño , Preescolar , Reparación del ADN , Femenino , Humanos , Masculino , Fosforilación , Radiación Ionizante , Adulto Joven
19.
Mutat Res ; 861-862: 503303, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33551104

RESUMEN

Acetaldehyde (AA) has been classified as a probable human carcinogen by the International Agency for Research on Cancer (IARC, WHO) and by the US Environmental Protection Agency due to its ability to cause tumours following inhalation or alcohol consumption in animals. Humans are constantly exposed to AA through inhalation from the environment through cigarette smoke, vehicle fumes and industrial emissions as well as by persistent alcohol ingestion. Individuals with deficiencies in the enzymes that are involved in the metabolism of AA are more susceptible to its toxicity and constitute a vulnerable human population. Studies have shown that AA induces DNA damage and cytogenetic abnormalities. A study was undertaken to elucidate the clastogenic effects induced by AA and any preceding DNA damage that occurs in normal human lung fibroblasts as this will further validate the detrimental effects of inhalation exposure to AA. AA exposure induced DNA damage, involving DNA double strand breaks, which could possibly occur at the telomeric regions as well, resulting in a clastogenic effect and subsequent genomic instability, which contributed to the cell cycle arrest. The clastogenic effect induced by AA in human lung fibroblasts was evidenced by micronuclei induction and chromosomal aberrations, including those at the telomeric regions. Co-localisation between the DNA double strand breaks and telomeric regions was observed, suggesting possible induction of DNA double strand breaks due to AA exposure at the telomeric regions as a new mechanism beyond the clastogenic effect of AA. From the cell cycle profile following AA exposure, a G2/M phase arrest and a decrease in cell viability were also detected. Therefore, these effects due to AA exposure via inhalation may have implications in the development of carcinogenesis in humans.


Asunto(s)
Acetaldehído/efectos adversos , Aberraciones Cromosómicas/inducido químicamente , Daño del ADN , Fibroblastos/patología , Inestabilidad Genómica , Pulmón/patología , Mutágenos/efectos adversos , Supervivencia Celular , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fase G2 , Humanos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Telómero
20.
Adv Exp Med Biol ; 1300: 231-257, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33523437

RESUMEN

Recurrent spontaneous abortion (RSA) is usually defined as three or more spontaneous abortions prior to 20-28 weeks gestation. RSA affects approximately 2-5% of all women of childbearing age, and it brings tremendous psychological and psychiatric trauma to the women and also results in economic burden. The causes could be female age, anatomical and chromosomal abnormalities, genetic, endocrinological, placental anomalies, infection, smoking and alcohol consumption, psychological factor, exposure to environmental factors such as heavy metal, environment pollution, and radiation.


Asunto(s)
Aborto Habitual , Aborto Espontáneo , Aborto Habitual/epidemiología , Aborto Habitual/etiología , Aborto Espontáneo/epidemiología , Consumo de Bebidas Alcohólicas , Aberraciones Cromosómicas , Femenino , Edad Gestacional , Humanos , Embarazo , Fumar
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