Unraveling chromosomal and genotoxic damage in individuals occupationally exposed to coal from underground mining.

Purpose: Coal mining is a vital sector in Colombia, contributing significantly to the nation's economy and the development of its regions. However, despite its importance, it has led to a gradual decline in the health of mine workers and nearby residents. While the adverse health effects of open-pit coal mining on exposed individuals have been well-documented in Colombia and globally, studies investigating genetic damage in underground coal miners are lacking. Methods: The aim of our study was to evaluate chromosomal and genotoxic damage, in peripheral blood samples from a group of underground coal miners and residents of areas exposed to coal, in the town of Samacá, Boyacá-Colombia, and in a group of unexposed individuals by using banding and molecular cytogenetic techniques, as well as cytokinesis block micronucleus assays. Results: Our results suggest that occupational exposure to coal induces chromosomal and genotoxic damage in somatic cells of underground coal miners. Chromosomal and genotoxic damage is an important step in carcinogenesis and the development of many other diseases. Our findings provide valuable insights into the effects of coal dust exposure on chromosomal integrity and genetic stability. Conclusion: Our pilot study suggests that occupational exposure to coal induces chromosomal damage in underground coal miners, highlighting the importance of validating these findings with a larger sample size. Our results highlight the need to implement prevention and protection measures, as well as educational programs for underground coal miners. Characterizing and estimating exposure risks are extremely important for the safety of people exposed occupationally and environmentally to coal and its derivatives.

Loss of heterozygosity impacts MHC expression on the immune microenvironment in CDK12-mutated prostate cancer.

BACKGROUND: In prostate cancer (PCa), well-established biomarkers such as MSI status, TMB high, and PDL1 expression serve as reliable indicators for favorable responses to immunotherapy. Recent studies have suggested a potential association between CDK12 mutations and immunotherapy response; however, the precise mechanisms through which CDK12 mutation may influence immune response remain unclear. A plausible explanation for immune evasion in this subset of CDK12-mutated PCa may be reduced MHC expression. RESULTS: Using genomic data of CDK12-mutated PCa from 48 primary and 10 metastatic public domain samples and a retrospective cohort of 53 low-intermediate risk primary PCa, we investigated how variation in the expression of the MHC genes affected associated downstream pathways. We classified the patients based on gene expression quartiles of MHC-related genes and categorized the tumors into "High" and "Low" expression levels. CDK12-mutated tumors with higher MHC-expressed pathways were associated with the immune system and elevated PD-L1, IDO1, and TIM3 expression. Consistent with an inflamed tumor microenvironment (TME) phenotype, digital cytometric analyses identified increased CD8 + T cells, B cells, γδ T cells, and M1 Macrophages in this group. In contrast, CDK12-mutated tumors with lower MHC expression exhibited features consistent with an immune cold TME phenotype and immunoediting. Significantly, low MHC expression was also associated with chromosome 6 loss of heterozygosity (LOH) affecting the entire HLA gene cluster. These LOH events were observed in both major clonal and minor subclonal populations of tumor cells. In our retrospective study of 53 primary PCa cases from this Institute, we found a 4% (2/53) prevalence of CDK12 mutations, with the confirmation of this defect in one tumor through Sanger sequencing. In keeping with our analysis of public domain data this tumor exhibited low MHC expression at the RNA level. More extensive studies will be required to determine whether reduced HLA expression is generally associated with primary tumors or is a specific feature of CDK12 mutated PCa. CONCLUSIONS: These data show that analysis of CDK12 alteration, in the context of MHC expression levels, and LOH status may offer improved predictive value for outcomes in this potentially actionable genomic subgroup of PCa. In addition, these findings highlight the need to explore novel therapeutic strategies to enhance MHC expression in CDK12-defective PCa to improve immunotherapy responses.

Phytochemical characterization, isolation, antioxidant and cytogenotoxic activity of leaves of Heliotropium elongatum (Lehm) I.M. Johnst.

Heliotropium elongatum is used to treat inflammation, cough, and flu. This study aimed to characterize the phytochemical profile and determine the total phenolic content (TPC), antioxidant and cytogenotoxic activity of the ethanolic extract (EE), and fractions of H. elongatum leaves. In the phytochemical profile analysis, organic acids, reducing sugars, flavonoids, saponins, anthraquinones, steroids/triterpenes, and depsides/depsidones were detected in the EE and/or fractions (hexanic/FH, chloroformic/FC, ethyl acetate/FAE, and hydromethanolic/FHM). The highest TPC and highest antioxidant activity (DPPH and ABTS) was detected in FHM. In FH, 16 compounds were identified by GC-MS, and ursolic acid was isolated by 1H NMR and 13C NMR. HPLC-DAD from EE, FAE, and FHM demonstrated characteristic wavelengths for flavonoids, flavonols, flavones, and anthraquinones. ESI-IT/MSn analysis of EE, FC, FAE, and FHM revealed alkaloids, steroids, terpenoids, flavonoids, and phenolic acids. In Allium cepa assay there was no significant cytotoxic effect initiated by EE (62.5 to 1,000 µg/ml), FHM (1,000 µg/ml), and FAE (62.5 µg/ml). Genotoxicity was evidenced only with EE at 500 and 1,000 µg/ml, and FHM (62.5 to 1,000 µg/ml) as evidenced by presence of micronuclei (MN) and nuclear buds (NB). Our results identified compounds of medicinal interest with antioxidant activity; however observed cytogenotoxic changes indicated the need for caution when using these compounds for therapeutic purposes.

Técnicas de citogenética para el estudio de las leucemias / Cytogenetic techniques for the study of leukemias

Introducción: La leucemia se define como un proceso clonal de células hematopoyéticas, que se origina cuando las células sanguíneas que se producen en la médula ósea, cambian y se multiplican sin control. Esta se caracteriza por su heterogeneidad genética y se explica a través de mecanismos causados por alteraciones cromosómicas utilizados en la práctica clínica diaria como biomarcadores útiles para el diagnóstico, el pronóstico o la predicción de respuesta al tratamiento. Objetivo: Describir las técnicas de citogenética convencional y molecular para el diagnóstico y seguimiento de las leucemias. Métodos: Se realizó una revisión de la literatura en inglés y español, a través del sitio web PubMed y el motor de búsqueda Google Académico, de artículos publicados en los últimos cinco años. Se hizo un análisis y resumen de la bibliografía revisada. Análisis y síntesis de la información: En el transcurso de los años la citogenética ha proporcionado información crucial para el diagnóstico y el pronóstico de las neoplasias hematológicas. Tanto las técnicas de citogenética convencional y molecular, como la hibridación in situ fluorescente, la hibridación in situ fluorescente multicolor, el cariotipo espectral, la hibridación genómica comparada y los microarreglos, participan en el reconocimiento de alteraciones cromosómicas y de genes, así como de interacciones involucradas en el proceso de oncogénesis. Conclusiones: Las técnicas de citogenética contribuyen al diagnóstico, a la estratificación pronóstica y a la aplicación del tratamiento según el tipo o subtipo de leucemia(AU)

Introduction: Leukemia is defined as a clonal process of hematopoietic cells, which occurs when blood cells that are produced in the bone marrow change and multiply uncontrollably. This is characterized by its genetic heterogeneity and is explained through mechanisms caused by chromosomal alterations that are used in daily clinical practice as useful biomarkers for diagnosis, prognosis or prediction of response to treatment. Objective: To describe the conventional and molecular cytogenetic techniques used for the diagnosis and monitoring of leukemias. Methods: A review of the literature in English and in Spanish was carried out, in the PubMed website and using the search engine Google, for articles published in the last five years. We performed analysis and summary of the reviewed bibliography. Analysis and synthesis of information: Cytogenetics over the years has provided crucial information for the diagnosis and prognosis of hematologic malignancies. Both conventional and molecular cytogenetic techniques such as fluorescent in situ hybridization, multicolor fluorescent in situ hybridization, spectral karyotype, comparative genomic hybridization and microarrays, participate in the recognition of chromosomal and gene alterations, as well as interactions involved in the oncogenesis process. Conclusions: These cytogenetic techniques contribute to the diagnosis, prognostic stratification and application of treatment according to the type or subtype of leukemia(AU)

Profile of Chromosomal Alterations, Chromosomal Instability and Clonal Heterogeneity in Colombian Farmers Exposed to Pesticides.

Pesticides are a group of environmental pollutants widely used in agriculture to protect crops, and their indiscriminate use has led to a growing public awareness about the health hazards associated with exposure to these substances. In fact, exposure to pesticides has been associated with an increased risk of developing diseases, including cancer. In a study previously published by us, we observed the induction of specific chromosomal alterations and, in general, the deleterious effect of pesticides on the chromosomes of five individuals exposed to pesticides. Considering the importance of our previous findings and their implications in the identification of cytogenetic biomarkers for the monitoring of exposed populations, we decided to conduct a new study with a greater number of individuals exposed to pesticides. Considering the above, the aim of this study was to evaluate the type and frequency of chromosomal alterations, chromosomal variants, the level of chromosomal instability and the clonal heterogeneity in a group of thirty-four farmers occupationally exposed to pesticides in the town of Simijacá, Colombia, and in a control group of thirty-four unexposed individuals, by using Banding Cytogenetics and Molecular Cytogenetics (Fluorescence in situ hybridization). Our results showed that farmers exposed to pesticides had significantly increased frequencies of chromosomal alterations, chromosomal variants, chromosomal instability and clonal heterogeneity when compared with controls. Our results confirm the results previously reported by us, and indicate that occupational exposure to pesticides induces not only chromosomal instability but also clonal heterogeneity in the somatic cells of people exposed to pesticides. This study constitutes, to our knowledge, the first study that reports clonal heterogeneity associated with occupational exposure to pesticides. Chromosomal instability and clonal heterogeneity, in addition to reflecting the instability of the system, could predispose cells to acquire additional instability and, therefore, to an increased risk of developing diseases.

Determination of phytotoxicity and cytogenotoxicity due to exposure to particles originating from sugarcane burning using test systems Lactuca sativa L. and Allium cepa L.

Sugarcane straw burning generates particulate matter with complex composition resulting in atmosphere pollution. Sugarcane straw sugarcane burning particles (PSSB) contain several chemical compounds that were previously identified to be associated with carcinogenic and mutagenic processes. The aim of the present study was to extract PSSB under lab conditions and subsequently determine phyto- and cytogenotoxicity of these particles using Lactuca sativa L. and Allium cepa L. bioassays. Seeds of lettuce var. Cinderela and onion cv. Vale-Ouro IPA-11 were germinated in Petri dishes containing different concentrations of PSSB at 25, 50, 100, 200 or 300 mg/ml as well as control for 72 hr. Seed germination of lettuce was inhibited by PSSB, in a concentration-dependent manner, accompanied by decreased root growth, suggesting phytotoxic effects. Further, reduction of mitotic index and high number of chromosomal alterations in onion of meristematics cells indicated a cytogenotoxic action attributed to PSSB. Although the chemical composition of PSSB in question has not been determined, the phyto- and cytogenotoxic effects may be linked to the possible presence of polycyclic aromatic hydrocarbons (PAHs), which are were identified as the main constituents of particulate matter resulting from burning of sugarcane straw, in addition to exerting adverse biological effects that might result in mutations and cancer. Data demonstrated that the use of plants bioassays might be an important tool for biomonitoring air quality.

Distribution of segmental chromosomal alterations in neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is a heterogeneous tumor with extremely diverse prognosis according to clinical and genetic factors such as specific combinations of chromosomal imbalances. METHODS: Molecular karyotyping data from a national neuroblastic tumor database of 155 NB samples were analyzed and related to clinical data. RESULTS: Segmental chromosomal alterations (SCA) were detected in 102 NB, whereas 45 only displayed numerical alterations. Incidence of SCA was higher in stage M (92%) and MYCN amplified (MNA) NB (96%). Presence of SCA was associated with older age, especially 1q gain and 3p deletion. 96% of the deaths were observed in the SCA group and 85% of the relapsed NB contained SCA. The alteration most commonly associated with a higher number of other segmental rearrangements was 11q deletion, followed by 4p deletion. Whole-chromosome 19 gain was associated with lower stages, absence of SCA and better outcome. CONCLUSIONS: SCA are not randomly distributed and are concentrated on recurrent chromosomes. The most frequently affected chromosomes identify prognostic factors in specific risk groups. SCA are associated with older age and MNA. We have identified a small subset of patients with better outcome that share whole-chromosome 19 numeric gain, suggesting its use as a prognostic biomarker in NB.

Detection of mosaicism for segmental and whole chromosome imbalances by targeted sequencing.

Mosaic segmental and whole chromosome copy number alterations are postzygotic variations known to be associated with several disorders. We have previously presented an efficient targeted sequencing approach to simultaneously detect point mutations and copy number variations (CNVs). In this study, we evaluated the efficiency of this approach to detect mosaic CNVs, using seven postnatal and 19 tumor samples, previously characterized by chromosomal microarray analyses (CMA). These samples harbored a total of 28 genomic imbalances ranging in size from 0.68 to 171 Mb, and present in 10-80% of the cells. All CNV regions covered by the platform were correctly identified in postnatal samples, and only seven out of 19 CNVs from tumor samples were not identified either because of a lack of target probes in the affected genomic regions or an absence of minimum reads for an alteration call. These results demonstrate that, in a research setting, this is a robust approach for detecting mosaicism in cases of segmental and whole chromosome alterations. Although the current sequencing platform presented a resolution similar to genomic microarrays, it is still necessary to further validate this approach in a clinical setting in order to replace CMA and sequencing analyses by a single test.

Actividad antimutagénica e identificación de compuestos antioxidantes en la planta Poincianella bracteosa (Fabaceae)

Introducción: Poincianella bracteosa (Tul.) L.P. Queiroz. (Fabaceae), conocida como catingueira, es tradicionalmente utilizada en la medicina para tratar diarrea, hepatitis y anemia. Sin embargo, no hay estudios sobre los efectos tóxico genéticos de la P. bracteosa. Objetivo: En el presente estudio se tuvo como objetivo investigar el perfil fitoquímico y el potencial mutagénico y antimutagénico del extracto acuoso de la cáscara de P. bracteosa en Allium cepa y Mus musculus. Métodos: El extracto de la cáscara fue diluido en agua destilada para fornecer las cuatro concentraciones (2, 4, 8 y 16 mg/ml) utilizadas en el bioensayo A. cepa y las tres dosis (10, 20 y 40 mg / Kg) fueron administradas a los ratones (5 animales por grupo). El perfil fito-químico fue realizado por el test colorimétrico para identificar los principales metabólitos secundarios en el extracto de la cáscara. Tras el tratamiento, 5 000 células meristemáticas fueron analizadas para determinar el índice mitótico, el promedio de alteraciones cromosómicas y el porcentaje de reducción de daños. Para ratones, tras 24, 48 y 72 h, la sangre de la cola de cada animal fue recolectado para la preparación de dos láminas por animal. Para cada animal, 2 000 eritrocitos normocromáticos por ratón fueron evaluados para establecer el número de micronúcleos y el efecto protector. Se analizaron los dados por el test de Kruskal-Wallis (P < 0.05). El estudio fito-químico del extracto detectó azúcares reductores y taninos. Resultados: Ninguna de las concentraciones del extracto fue citotóxica y en todos los tratamientos (pre, simultáneo y después) fue observado el efecto citoprotetor en A. cepa. El promedio total de las alteraciones cromosómicas en todas las concentraciones apuntó actividad no mutagénica de la cáscara. El porcentaje de reducción del daño fue observada en los tratamientos pre (de 77.6 al 90.5 %), simultáneo (del 95.6 al 114.7 %) y tras (de 84.8 al 117.7 %). En los ratones, ninguna de las dosis del extracto presentó efecto mutagénico y el porcentaje de reducción del daño osciló de -21.2 al 78.6 % (pre); de 27.5 al 101.3 % (simultánea) y de 85.5 al 120.6 % (tras-tratamiento). Probablemente, los fito-químicos presentes en el extracto no interfirieron en el ciclo celular (A. cepa), tampoco causaron daños al DNA (A. cepa y ratones) y presentaron efecto protector en las dos especies estudiadas. Los datos observados apuntan la importancia del extracto de la cáscara de P. bracteosa para inhibición del daño y quimio prevención. Sin embargo, más estudios deben ser realizados para garantizar su efecto protector sobre el material genético.

Introduction: Poincianella bracteosa (Tul.) L.P. Queiroz. (Fabaceae), known as catingueira, is traditionally used in medicine to treat diarrhea, hepatitis and anemia. However, there are no studies on their toxicogenetic effects. Objective: The present study aimed to investigate the phytochemical profile as well as the mutagenic and antimutagenic potential of P. bracteosa aqueous bark extract in Allium cepa and Mus musculus. Methods: The extract from barks was diluted in distilled water to yield the four concentrations (2, 4, 8 and 16 mg/ml) used in the A. cepa bioassay and the three doses (10, 20 and 40 mg/Kg) administered to the mice (five animals per group). The phytochemical profile was performed by the colorimetric test to identify the main secondary metabolites in the bark extract. After treatment, five-thousand meristematic cells were analyzed to determine the mitotic index, the mean number of chromosome alterations and the percentage of damage reduction. For mice, after 24, 48 and 72 h, tail blood was collected from each animal for the preparation of two slides per animal. For each animal, 2 000 normochromatic erythrocytes per mice were evaluated to establish the number of micronuclei and the protective effect. Data were analyzed by Kruskal-Wallis test (P < 0.05). Results: The phytochemical analysis of the extract detected reducing sugars and tannins. None of the concentrations of extract was cytotoxic and the cytoprotective effect was observed in A. cepa for all treatments (pre-, simultaneous and post-). The total mean of chromosome alterations in all concentrations indicated a non-mutagenic activity of the bark. The percentage of damage reduction was observed in the pre- (77.6 to 90.5 %), simultaneous (95.6 to 114.7 %) and post- (84.8 to 117.7 %) treatments. In mice, none of the dosages of extract presented mutagenic effect and the percentage of damage reduction varied from -21.16 to 78.63 % (pre-); from 27.51 to 101.28 % (simultaneous) and from 85.47 to 120.63 % (post-treatment). Conclusions: Probably, the phytochemicals in the extract did not interfere with the cell cycle (A. cepa) nor caused damage to the DNA (A. cepa and mice), and exhibited protective effect in both studied species. The observed data indicate the importance of P. bracteosa bark extract for the inhibition of damage and chemoprevention. However, more studies should be carried out to ensure its protective effect on the genetic material.

Marinobufagin, a molecule from poisonous frogs, causes biochemical, morphological and cell cycle changes in human neoplasms and vegetal cells.

Skin toad secretion present physiologically active molecules to protect them against microorganisms, predators and infections. This work detailed the antiproliferative action of marinobufagin on tumor and normal lines, investigate its mechanism on HL-60 leukemia cells and its toxic effects on Allium cepa meristematic cells. Initially, cytotoxic action was assessed by colorimetric assays. Next, HL-60 cells were analyzed by morphological and flow cytometry techniques and growing A. cepa roots were examined after 72 h exposure. Marinobufagin presented high antiproliferative action against all human tumor lines [IC50 values ranging from 0.15 (leukemia) to 7.35 (larynx) µM] and it failed against human erythrocytes and murine lines. Human normal peripheral blood mononuclear cells (PBMC) were up to 72.5-fold less sensitive [IC50: 10.88 µM] to marinobufagin than HL-60 line, but DNA strand breaks were no detected. Leukemia treaded cells exhibited cell viability reduction, DNA fragmentation, phosphatidylserine externalization, binucleation, nuclear condensation and cytoplasmic vacuoles. Marinobufagin also reduced the growth of A. cepa roots (EC50: 7.5 µM) and mitotic index, caused cell cycle arrest and chromosomal alterations (micronuclei, delays and C-metaphases) in meristematic cells. So, to find out partially targeted natural molecules on human leukemia cells, like marinobufagin, is an amazing and stimulating way to continue the battle against cancer.

Crecimiento intrauterino restringido como síntoma guía para el diagnóstico genético prenatal del síndrome de Wolf-Hirschhorn en gestación gemelar bicorial biamniótica / Restricted Intrauterine Growth as a Guiding Symptom for Prenatal Genetic Diagnosis of Wolf-Hirschhorn Syndrome in Bicorial Diamniotic Twin Gestation

El síndrome de Wolf Hirschhorn, también conocido como monosomía del brazo corto del cromosoma 4 (4p) o síndrome 4p-, es una rara enfermedad genética descrita por primera vez en el año 1961 por los doctores Cooper y Hirschhorn. El objetivo del trabajo es presentar un caso clínico sobre el síndrome de Wolf-Hirschhorn, que es un trastorno genético raro y aún bastante desconocido que cursa con múltiples anomalías morfológicas congénitas, así como con un retraso neurológico e intelectual de grado variable. La prevalencia de este síndrome es extremadamente baja, teniendo en cuenta que la cifra puede estar infraestimada, dada las pérdidas gestacionales precoces y la dificultad en el diagnóstico prenatal. Reportamos el caso de una paciente con gestación gemelar bicorial biamniótica tras un ciclo de FIV-ICSI, en el que al segundo gemelo se diagnosticó un Síndrome de Wolf-Hirschhorn, luego del estudio por una discordancia de pesos estimados y crecimiento intrauterino restringido de este segundo feto. El patrón clásico de presentación clínica se caracteriza por el desarrollo de alteraciones craneofaciales importantes, retraso en el crecimiento normal tanto prenatal como posnatal y deficiencia mental e intelectual de grado variable. El diagnóstico prenatal debe ser realizado por expertos. Puede sospecharse por un crecimiento intrauterino restringido, ya que se da en 80-90 por ciento de los fetos con esta patología. Una vez diagnosticado, se recomienda el estudio genético de los padres, dado que hasta 15 por ciento de los progenitores pueden padecer un reordenamiento cromosómico equilibrado en el brazo corto del cromosoma 4(AU)

Wolf Hirschhorn syndrome, also known as monosomy of the short arm of chromosome 4 (4p) or 4p-syndrome, is a rare genetic disorder first described in 1961 by doctors Cooper and Hirschhorn. The prevalence of this syndrome is extremely low, taking into account that the figure may be underestimated given the early gestational losses and the difficulty in prenatal diagnosis. The objective of the study is to present a clinical case of Wolf-Hirschhorn syndrome, presenting with multiple congenital morphological anomalies, as well as a neurological and intellectual retardation of variable degree. We report the case of a patient with a bicorial biamniotic twin gestation after a cycle of IVF-ICSI. The second twin was diagnosed with a Wolf-Hirschhorn syndrome, after performing the corresponding study due to a discordance of estimated weights and restricted intrauterine growth of this second fetus. The development of important craniofacial alterations, delay of normal prenatal and postnatal growth, and mental and intellectual deficiency of variable degree characterize the classic clinical presentation. Experts must make prenatal diagnosis. Wolf-Hirschhorn syndrome can be suspected by a restricted intrauterine growth, as it occurs in 80-90 percent of fetuses with this pathology. Once diagnosed, the genetic study of the parents is recommended, since up to 15 percent of the parents can suffer a balanced chromosomal rearrangement in the short arm of chromosome 4(AU)

Effect of SPL (Spent Pot Liner) and its main components on root growth, mitotic activity and phosphorylation of Histone H3 in Lactuca sativa L.

Spent Pot Liner (SPL) is a solid waste from the aluminum industry frequently disposed of in industrial landfills; it can be leached and contaminate the soil, sources of drinking water and plantations, and thus may pose a risk to human health and to ecosystems. Its composition is high variable, including cyanide, fluoride and aluminum salts, which are highly toxic and environmental pollutants. This study evaluated the effect of SPL and its main components on root growth and the mitosis of Lactuca sativa, by investigating the mechanisms of cellular and chromosomal alterations with the aid of immunolocalization. To this end, newly emerged roots of L. sativa were exposed to SPL and its main components (solutions of cyanide, fluoride and aluminum) and to calcium chloride (control) for 48h. After this, root length was measured and cell cycle was examined by means of conventional cytogenetics and immunolocalization. Root growth was inhibited in the treatments with SPL and aluminum; chromosomal and nuclear alterations were observed in all treatments. The immunolocalization evidenced normal dividing cells with regular temporal and spatial distribution of histone H3 phosphorylation at serine 10 (H3S10ph). However, SPL and its main components inhibited the phosphorylation of histone H3 at serine 10, inactivated pericentromeric regions and affected the cohesion of sister chromatids, thus affecting the arrangement of chromosomes in the metaphase plate and separation of chromatids in anaphase. In addition, these substances induced breaks in pericentromeric regions, characterized as fragile sites.

Análise citogenética em material de abortamento espontâneo / Cytogenetic analysis of material from spontaneous abortion

OBJETIVO: Descrever as anormalidades cromossômicas em material de abortamento espontâneo. MÉTODOS: Realizou-se compilação retrospectiva da análise de cariótipo em lâmina corada com Banda G por microscopia óptica e em material de 428 produtos de abortamento encaminhados para estudo. RESULTADOS: Foram observados 145 resultados normais (33,9 por cento) e 237 resultados anormais (55,4 por cento). Em 46 amostras não houve crescimento celular (10,7 por cento). As anormalidades numéricas foram as mais frequentes, destacando-se a trissomia do 16 (41 casos), a triplodia (27 casos), a monossomia do X (26 casos), a tetraploidia (13 casos) e a trissomia do 15 (13 casos). CONCLUSÃO: As alterações citogenéticas representam importante causa de perdas gestacionais e sua detecção auxilia o aconselhamento genético do casal. A trissomia do cromossomo 16 é a alteração mais frequentemente encontrada.

OBJECTIVE: To describe chromosomal abnormalities in spontaneous abortion material. METHODS: A retrospective compilation of karyotype analysis of slides stained with Band G was carried out by optical microscopy with materials of 428 abortion products referred for study. RESULTS: There were 145 normal results (33.9 percent) and 237 abnormal results (55.4 percent). In 46 samples there was no cell growth (10.7 percent). Numerical abnormalities were the most frequent, especially trisomy 16 (41 cases), triplodia (27 cases), monosomy X (26 cases), tetraploidy (13 cases) and trisomy 15 (13 cases). CONCLUSION: Cytogenetic alterations are an important cause of pregnancy loss and their detection helps the genetic counseling to the couple. Trisomy 16 is the most often found change.

Alteraciones cromosómicas estructurales inducidas por bioflavonoides de la dieta en linfocitos de anemia de Fanconi / Structural Chromosomal Alterations Induced by Dietary Bioflavonoids in Fanconi Anemia Lymphocytes

Introducción. La anemia de Fanconi es una enfermedad genética con herencia autosómica recesiva caracterizada por aplasia medular, predisposición a leucemia mieloide aguda, tumores sólidos y aumento en la inestabilidad cromosómica. Este síndrome puede considerarse como modelo biológico para analizar sustancias naturales con posible efecto genotóxico, difíciles de evaluar en células normales. Los objetivos de este estudio son describir y cuantificar las alteraciones cromosómicas estructurales inducidas por cinco flavonas, dos isoflavonas y una droga quimioterapéutica inhibidora de la topoisomerasa II, en cultivos de linfocitos de anemia de Fanconi a fin de determinar si existe un incremento en el número y tipo de daño cromosómico respecto al control. Materiales y métodos. Se analizaron los cromosomas de linfocitos estimulados con fitohemaglutinina M de una paciente con anemia de Fanconi. Se evaluaron 100 metafases de cada uno de los cultivos expuestos a las sustancias y control basal. Las alteraciones cromosómicas fueron documentadas con fotografías convencionales y digitales mediante analizador de imágenes. Se utilizó la prueba de c2 para determinar diferencias significativas entre el daño cromosómico entre cultivos expuestos y no expuestos con un valor de P <0,05. Resultados. Se encontraron 431 alteraciones cromosómicas en 1000 metafases analizadas; la genisteína tuvo el mayor efecto genotóxico, seguida de la genistina, fisetina, kaenferol, quercetina, baicaleína y miricetina. Las anomalías más frecuentes fueron las rupturas cromatídicas, rupturas cromosómicas, brechas (gaps) cromatídicas y cromosómicas, intercambios cuadri-radiales, cromosomas dicéntricos y rearreglos complejos. Conclusión. Los bioflavonoides genisteína, genistina y fisetina, presentes comúnmente en la dieta, aumentaron el número de alteraciones cromosómicas de manera significativa respecto al control en linfocitos de anemia de Fanconi.

Introduction. Fanconi anemia is an autosomal recessive disease characterized by a variety of congenital abnormalities, progressive bone marrow failure, increased chromosomal instability and higher risk to acute myeloid leukemia, solid tumors. This entity can be considered an appropriate biological model to analyze natural substances with possible genotoxic effect. The aims of this study were to describe and quantify structural chromosomal aberrations induced by 5 flavones,² isoflavones and a topoisomerase II chemotherapeutic inhibitor in Fanconi anemia lymphocytes in order to determine chromosomal numbers changes and/ or type of chromosomal damage. Materials and methods. Chromosomes stimulated by phytohaemagglutinin M, from Fanconi anemia lymphocytes, were analysed by conventional cytogenetic culture. For each chemical substance and controls, one hundred metaphases were evaluated. Chromosomal alterations were documented by photography and imaging analyzer. To statistical analysis was used chi square test to identify significant differences between frequencies of chromosomal damage of basal and exposed cell cultured a P value less than 0.05. Results. There were 431 chromosomal alterations in 1000 metaphases analysed; genistein was the more genotoxic bioflavonoid, followed in descendent order by genistin, fisetin, kaempferol, quercetin, baicalein and miricetin. Chromosomal aberrations observed were: chromatid breaks, chromosomal breaks, cromatid and chromosomal gaps, quadriratials exchanges, dicentrics chromosome and complex rearrangements. Conclusion. Bioflavonoids as genistein, genistin and fisetin, which are commonly present in the human diet, showed statistical significance in the number of chromosomal aberrations in Fanconi anemia lymphocytes, regarding the basal damage.

Unexpected chromosomal alterations in Tayassu tajacu (Artiodactyla: Tayassuidae) in captivity / Alterações cromossômicas inesperadas em Tayassu tajacu (Artiodactyla: tayassuidae) de cativeiros

Os animais silvestres têm sido utilizados como bioindicadores quando o ambiente é exposto a estressores químicos. Em geral, os agentes químicos podem induzir às alterações cromossômicas dos tipos falhas e quebras. Tayassu tajacu, é uma espécie aparentada dos porcos verdadeiro e apresenta uma grande estabilidade cariotípica. As únicas alterações descritas são em relação a forma do cromossomo X. Foram observadas falhas e quebras cromossômicas durante as análise citogenética. Estas alterações foram detectadas em cromossomos autossômicos. Levantamentos realizados na literatura associados as dados observados nos exemplares estudados, indicam um vermífugo, a base de ivermectina, como o possível causador dessas alterações cromossômicas. (AU)

Wild animals have been used as bioindicators in situations in which the environment was exposed to chemical agents. In general, chemical agents may induce chromosomal aberrations, such as breaks and gaps. The peccary, Tayassu tajacu is a pig relative that exhibits a very stable karyotype with the only described alterations being of the form of the X chromosome. Chromosomal gaps and breaks were observed at high frequencies during cytogenetics analyses. These alterations were observed in the chromosomes autossomics. Reviews of the literature and of the data described herein suggests that an vermifuge, the ivermectin base, was the most likely cause of these chromosomal alterations. (AU)