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(4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (PHT) belongs to the phenstatin family. This compound has been studied due to its potent cytotoxicity and ability to inhibit tubulin assembly. The present study aimed to evaluate the mutagenic potential of PHT in human lymphocytes. PHT displayed cytotoxicity in human lymphocytes with an IC50 value of 5.68 μM, and therefore, concentrations of 0.25, 0.5, 1.0, 2.0, and 4.0 μM were used for all protocols. The alkaline comet assay and chromosome aberration (CA) analysis were performed in different phases of the cell cycle (G1, G1/S, transition, and G2), to evaluate the DNA-damaging and clastogenic effects of PHT, respectively. CA analysis was carried out in the presence or absence of colchicine to evaluate the action of PHT in the mitotic phase. PHT was cytotoxic and significantly reduced the mitotic index with drug exposure in all phases of cell cycle. Interestingly, it induced an increase in mitotic index in experimental protocols without colchicine, corroborating its action as an antitubulin agent. It also induced DNA damage and was clastogenic with drug exposure in all phases of the cell cycle, in the presence or absence of colchicine. In conclusion, PHT induces DNA damage and exerts clastogenic effects in human lymphocytes., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

We evaluated whether MYC, TP53, and chromosome 17 copy-number alterations occur in ACP02, ACP03, and AGP01 gastric cancer cell lines and in their tumor counterpart. Fluorescence in situ hybridization for MYC and TP53 genes and for chromosome 17 was applied in the 6th, 12th, 60th, and 85th passages of the cell lines and in their parental primary tumors. We observed that three and four MYC signals were the most common alterations in gastric cell lines and tumors. ACP02 presented cells with two copies of chr17 and loss of one copy of TP53 more frequently than ACP03 and AGP01. Only ACP03 and AGP01 presented clonal chr17 trisomy with three or two TP53 copies. The frequency of MYC gain, TP53 loss, and chromosome 17 trisomy seems to increase in gastric cell lines compared to their parental tumors. Our findings reveal that these cell lines retain, in vitro, the genetic alterations presented in their parental primary tumors.

Uranium is a natural radioactive metallic element; its effect on the organism is cumulative, and chronic exposure to this element can induce carcinogenesis. Three cities of the Amazon region-Monte Alegre, Prainha, and Alenquer-in North Brazil, are located in one of the largest uranium mineralization areas of the world. Radon is a radioactive gas, part of uranium decay series and readily diffuses through rock. In Monte Alegre, most of the houses are built of rocks removed from the Earth's crust in the forest, where the uranium reserves lie. The objective of the present work is to determine the presence or absence of genotoxicity and risk of carcinogenesis induced by natural exposure to uranium and radon in the populations of these three cities. The frequency of micronuclei (MN) and chromosomal aberrations (CA) showed no statistically significant differences between the control population and the three study populations (P > 0.05). MN was also analyzed using the fluorescence in situ hybridization (FISH) technique, with a centromere-specific probe. No clastogenic and/or aneugenic effects were found in the populations. Using FISH analysis, other carcinogenesis biomarkers were analyzed, but neither the presence of the IGH/BCL2 translocation nor an amplification of the MYC gene and 22q21 region was detected. Clastogenicity and DNA damage were also not found in the populations analyzed using the alkaline comet assay. The mitotic index showed no cytotoxicity in the analyzed individuals' lymphocytes. Once we do not have data concerning radiation doses from other sources, such as cosmic rays, potassium, thorium, or anthropogenic sources, it is hard to determine if uranium emissions in this geographic region where our study population lives are too low to cause significant DNA damage. Regardless, genetic analyses suggest that the radiation in our study area is not high enough to induce DNA alterations or to interfere with mitotic apparatus formation. It is also possible that damages caused by radiation doses undergo cellular repair.

The identification of cytogenetic abnormalities in schizophrenic patients may provide clues to the genes involved in this disease. For this reason, a chromosomal analysis of samples from 62 schizophrenics and 70 controls was performed with trypsin-Giemsa banding and fluorescence in situ hybridization of the X chromosome. A clonal pericentric inversion on chromosome 9 was detected in one male patient, and we also discovered mosaicism associated with X chromosome aneuploidy in female patients, primarily detected in schizophrenic and normal female controls over 40 years old. When compared with age-matched female controls, the frequency of X chromosome loss was not significantly different between schizophrenics and controls, except for the 40- to 49-year-old age group. Our findings suggest that the X chromosome loss seen in schizophrenic patients is inherent to the normal cellular aging process. However, our data also suggest that X chromosome gain may be correlated with schizophrenia in this Brazilian population.

Background: This study evaluates the existence of numerical alterations of chromosome 17 and TP53 gene deletion in gastric adenocarcinoma. The p53 protein expression was also evaluated, as well as, possible associations with clinicopathological characteristics., Methods: Dual-color fluorescence in situ hybridization and immunostaining were performed in twenty gastric cancer samples of individuals from Northern Brazil., Results: Deletion of TP53 was found in all samples. TP53 was inactivated mainly by single allelic deletion, varying to 7-39% of cells/case. Aneusomy of chromosome 17 was observed in 85% of cases. Chromosome 17 monosomy and gain were both observed in about half of cases. Cells with gain of chromosome 17 frequently presented TP53 deletion. The frequency of cells with two chr17 and one TP53 signals observed was higher in diffuse than in intestinal-type GC. Immunoreactivity of p53 was found only in intestinal-type samples. The frequency of cells with two chr17 and two TP53 signals found was higher in samples with positive p53 expression than in negative cases in intestinal-type GC., Conclusion: We suggest that TP53 deletion and chromosome 17 aneusomy is a common event in GC and other TP53 alterations, as mutation, may be implicated in the distinct carcinogenesis process of diffuse and intestinal types.

Gastric adenocarcinoma is a serious public health concern, especially in northern Brazil. Gastric cancer can be subdivided into diffuse and intestinal types. Genetic imbalances in diffuse-type gastric cancer remain largely unknown. In the present study, we analyzed 24 advanced diffuse-type gastric cancer samples from northern Brazil subjects using high-resolution comparative genomic hybridization. We found chromosomal alterations in 75% of samples. In cancers with aneusomies, the mean genomic copy number alteration was 6.4. Losses of chromosome regions exceeded gains. The most frequent losses were located at chromosome regions 11q and 18q (five samples for each region), 1pq, 3q, 4q, 5q, 13q, and 14q (four samples), followed by 2pq, 7p, 9pq, 11p, and 16p (three samples). Our results confirm that gastric cancer has a complex pattern of chromosomal alterations that can be due to general chromosomal instability related to the advanced stage of gastric carcinogenesis. Loss of 11q and 18q were the most frequent chromosomal changes in diffuse-type gastric adenocarcinoma in individuals from northern Brazil. Frequent loss of 11q chromosome region in this gastric cancer may be peculiar among this population.

Sources of light beams such as white fluorescent light, are present in our daily life to meet the needs of life in the modern world. This study was conducted with the objective of determining the possible genotoxic, cytotoxic and aneugenic effects caused by this agent in different stages of the cell cycle (G0/early G1, S, and late G2), using different cytogenetic parameters (sister chromatid exchanges--SCE, chromosome aberrations--CA, and detection of aneugenic effects) in lymphocytes from temporary cultures of human peripheral blood. WFL showed a genotoxic effect in vitro, expressed by an increase in the frequency of SCE's, regardless of the cell cycle stage. However, no increase in the frequency of CAs was observed. In addition, disturbances in cell cycle kinetics and chromosomal segregation were also observed. Taken together, such data may contribute to a better understanding and a different management in the use of phototherapy for some pathological conditions.

Gastric cancer is the second leading cause of death by cancer in Brazil. Early gastric cancer represents approximately 10% of gastric cancer cases in some services of Brazil, which underscores the need for early gastric cancer diagnosis that could lead to better prognosis. There are few published studies of cytogenetic alterations in early gastric cancer. To evaluate MYC copy number and its protein expression, we performed fluorescence in situ hybridization and immunohistochemical analyses in five early gastric adenocarcinomas in individuals from northern Brazil. Three signals of MYC and MYC immunoreactivity were observed in all five samples, regardless of histologic type, tumor extension, or lymph nodal status. These novel findings concerning MYC copy number alteration in early gastric cancer suggest that MYC alteration is observed in the beginning of gastric carcinogenesis and could be used as a therapeutic target.

Gastric cancer is the third most frequent type of neoplasia and the second most important cause of cancer-related death in the world. In northern Brazil, the state of Pará shows a high incidence of this disease and the capital ranks among cities with the highest incidence of stomach cancer in the world. To evaluate chromosomal aberrations implicated in gastric carcinogenesis, we analyzed 16 samples of gastric adenocarcinoma by fluorescence in situ hybridization using a chromosome 8 alpha-satellite probe and by direct chromosomal analysis techniques. All lesions were classified as at advanced stages according to the recommendations of the Union Internationale Contre le Cancer (UICC). Trisomy 8 was the main finding of this study, observed in all cases. There was no significant difference between chromosome 8 ploidy and localization, stage, or histological type of adenocarcinoma in our sample. The high incidence of alterations we found in chromosome 8 may be a regional characteristic, related to the high incidence of this neoplasm in Pará state and a strong influence of external factors, such as eating habits. This aberration may comprise a cytogenetic subgroup of this neoplasm. Additional investigations are necessary to confirm the involvement of chromosome 8 and to identify genes in this chromosome related to gastric carcinogenesis.

Background: The genetic events involved in gastric cancer, the third most frequent cancer in the world with a high incidence in Pard State, Brazil, remain largely unknown., Materials and Methods: Twenty-one primary gastric adenocarcinomas were investigated by comparative genomic hybridization (CGH) and the relationships between genomic abnormalities and histopathological features were evaluated., Results: Eighty-one percent of cases presented DNA copy-number changes. Chromosomal gains were the most frequent finding, losses occurring only in the diffuse type. The main copy-number gains were on chromosome 8, principally on 8q24.1 (8/21 cases), 8p21 (3/21) and 8p23.2-8p12 (2/21). Gain of region 8q24. 1, where C-MYC is located, was the main finding, exclusively in the intestinal type with metastasis., Conclusion: C-MYC locus amplification may be predictor of aggressiveness in intestinal-type gastric cancer, playing an important role in its development and progression. Moreover, other genes on 8q24 should be investigated. Gastric adenocarcinomas of differing histopathological features were associated with distinct genetic alterations, supporting the hypothesis that they evolve through distinct genetic pathways.

Very satisfactory results have been obtained with the treatment of sickle cell anaemia with hydroxyurea (HU), an antineoplastic drug. This is because it significantly increases the levels of foetal haemoglobin. Nevertheless, inadequate dosages or prolonged treatment with this pharmaceutical can provoke cytotoxicity or genotoxicity, increasing the risk of neoplasia. We monitored patients under treatment with HU for possible mutagenic effects, through cytogenetic tests (mitotic index and chromosome aberrations) for one year. Checking at two-month intervals, the cytotoxic effect was not evident. There was no evidence of genotoxicity under the conditions of our experiment. However individuals treated with HU should be constantly monitored, as an absence of genotoxicity could be transitory; the mitotic index should also be observed, as an indicator of cytotoxicity.

Rotenone is a heterocyclic compound widely used as an insecticide, acaricide and piscicide. Its toxicity is mainly caused by the inhibition of mitochondrial respiratory processes and ATP production, resulting in the generation of reactive oxygen species. Reactive oxygen species can interact with DNA, RNA and proteins, leading to cell damage, followed by death. We used the Comet assay, and we analyzed chromosome aberrations, in order to evaluate the genotoxic and clastogenic effects of rotenone on the different phases of the cell cycle. Cultured human lymphocytes were treated with 1.0, 1.5 and 2.0 microg/mL rotenone during the G1, G1/S, S (pulses of 1 and 6 h), and G2 phases of the cell cycle. Rotenone induced DNA damage and was clastogenic, but the clastogenicity was detected only with treatments conducted during the G1/S and S phases of the cell cycle. Rotenone also induced endoreduplication and polyploidy in treatments made during G1, while it significantly reduced the mitotic index in all phases of the cell cycle.

Hydroxyurea is considered an antineoplastic drug, which also plays an important role in the treatment of sickle cell anemia patients. We evaluated and compared the clastogenic and cytotoxic effects of hydroxyurea, using chromosomal aberrations and mitotic index, respectively, as endpoints. In vitro short-term cultures of lymphocytes were exposed to several concentrations of this drug, at various cell cycle phases. There was a significant increase in the cytotoxicity of hydroxyurea at G1 and G1/S as well in the G2 phase of the cell cycle. Hydroxyurea did not significantly increase chromosome aberrations. There was an S-dependent cytotoxic effect of hydroxyurea, which is expected based on the known activity of hydroxyurea as an inhibitor of ribonucleotide reductase.

Twelve breast fibroadenomas were analyzed cytogenetically and only four were found to have clonal alterations. The presence of chromosomal alterations in fibroadenomas must be the consequence of the proliferating process and must not be related to the etiology of this type of lesion. In contrast, the few fibroadenomas that exhibit chromosomal alterations are likely to be those presenting a risk of neoplastic transformation. Clonal numerical alterations involved chromosomes 8, 18, 19, and 21. Of the chromosomal alterations found in the present study, only monosomy of chromosomes 19 and 21 has been reported in breast fibroadenomas. The loss of chromosome 21 was the most frequent alteration found in our sample. The study of benign proliferations and their comparison with chromosome alterations in their malignant counterparts ought to result in a better understanding of the genes acting on cell proliferation alone, and of the genes that cause these cells to exhibit varied behaviors such as recurrences, spontaneous regression and fast growth.

The mercury rejected in the water system, from mining operations and lixiviation of soils after deforestation, is considered to be the main contributors to the contamination of the ecosystem in the Amazon Basin. The objectives of the present study were to examine cytogenetic functions in peripheral lymphocytes within a population living on the banks of the Tapajós River with respect to methylmercury (MeHg) contamination, using hair mercury as a biological indicator of exposure. Our investigation shows a clear relation between methylmercury contamination and cytogenetic damage in lymphocytes at levels well below 50 micrograms/gram, the level at which initial clinical signs and symptoms of mercury poisoning occur. The first apparent biological effect with increasing MeHg hair level was the impairment of lymphocyte proliferation measured as mitotic index (MI). The relation between mercury concentration in hair and MI suggests that this parameter, an indicator of changes in lymphocytes and their ability to respond to culture conditions, may be an early marker of cytotoxicity and genotoxicity in humans and should be taken into account in the preliminary evaluation of the risks to populations exposed in vivo. This is the first report showing clear cytotoxic effects of long-term exposure to MeHg. Although the results strongly suggest that, under the conditions examined here, MeHg is both a spindle poison and a clastogen, the biological significance of these observations are as yet unknown. A long-term follow-up of these subjects should be undertaken.

Generally, benign breast lesions behave like innocuous and limited proliferations; however, sometimes they can represent precancerous pathologies. The cytogenetic analysis of five mammary epithelial hyperplasias is reported. Four cases had clonal chromosome alterations. All of the cases presented a modal number of 46 chromosomes. Chromosome 9 monosomies and chromosome 1 deletions were common in these benign tumors. The study of benign proliferations of the breast may reveal a possible relationship between chromosomal alterations and the conditions of the tissue.

The cytogenetic analysis of five mammary epithelial hyperplasias is reported. Only two cases had clonal chromosome alterations. Structural alterations involved chromosomes 1 and 5. Numerical alterations involved chromosomes X, 1, 6, 9, and 19. In four cases, the modal number was in the diploid range, and one case was tetraploid. The study of benign proliferations and their comparison with the chomosome alterations of their malignant counterparts could lead to a better understanding of the genes acting solely in cell proliferation and those that cause these cells to undergo malignant transformation and to become invasive.