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Chromosome Aberrations (chromosome + aberration)
Kinds of Chromosome Aberrations Selected AbstractsDefinitive molecular cytogenetic characterization of 15 colorectal cancer cell lines,GENES, CHROMOSOMES AND CANCER, Issue 3 2010Turid Knutsen In defining the genetic profiles in cancer, cytogenetically aberrant cell lines derived from primary tumors are important tools for the study of carcinogenesis. Here, we present the results of a comprehensive investigation of 15 established colorectal cancer cell lines using spectral karyotyping (SKY), fluorescence in situ hybridization, and comparative genomic hybridization (CGH). Detailed karyotypic analysis by SKY on five of the lines (P53HCT116, T84, NCI-H508, NCI-H716, and SK-CO-1) is described here for the first time. The five lines with karyotypes in the diploid range and that are characterized by defects in DNA mismatch repair had a mean of 4.8 chromosomal abnormalities per line, whereas the 10 aneuploid lines exhibited complex karyotypes and a mean of 30 chromosomal abnormalities. Of the 150 clonal translocations, only eight were balanced and none were recurrent among the lines. We also reviewed the karyotypes of 345 cases of adenocarcinoma of the large intestine listed in the Mitelman Database of Chromosome Aberrations in Cancer. The types of abnormalities observed in the cell lines reflected those seen in primary tumors: there were no recurrent translocations in either tumors or cell lines; isochromosomes were the most common recurrent abnormalities; and breakpoints occurred most frequently at the centromeric/pericentromeric and telomere regions. Of the genomic imbalances detected by array CGH, 87% correlated with chromosome aberrations observed in the SKY studies. The fact that chromosome abnormalities predominantly result in copy number changes rather than specific chromosome or gene fusions suggests that this may be the major mechanism leading to carcinogenesis in colorectal cancer. Published 2009 Wiley-Liss, Inc. [source] A pooled analysis of karyotypic patterns, breakpoints and imbalances in 783 cytogenetically abnormal multiple myelomas reveals frequently involved chromosome segments as well as significant age- and sex-related differencesBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2003Thérèse Nilsson Summary. The cytogenetic features (ploidy, complexity, breakpoints, imbalances) were ascertained in 783 abnormal multiple myeloma (MM) cases to identify frequently involved chromosomal regions as well as a possible impact of age/sex. The series included MM patients from the Mitelman Database of Chromosome Aberrations in Cancer and from our own laboratory. Hyperdiploidy was most common, followed by hypodiploidy, pseudodiploidy and tri-/tetraploidy. Most cases were complex, with a median of eight changes per patient. The distribution of modal numbers differed between younger and older patients, but was not related to sex. No sex- or age-related differences regarding the number of anomalies were found. The most frequent genomic breakpoints were 14q32, 11q13, 1q10, 8q24, 1p11, 1q21, 22q11, 1p13, 1q11, 19q13, 1p22, 6q21 and 17p11. Breaks in 1p13, 6q21 and 11q13 were more common in the younger age group. The most frequent imbalances were +,9, ,,13, +,15, +,19, +,11 and ,,Y. Trisomy 11 and monosomy 16 were more common among men, while ,X was more frequent among women. Loss of Y as the sole change and +,5 were more common in elderly patients, and ,,14 was more frequent in the younger age group. The present findings strongly suggest that some karyotypic features of MM are influenced by endogenous and/or exogenous factors. [source] Gender differences in genetic damage induced by the tobacco-specific nitrosamine NNK and the influence of the Thr241Met polymorphism in the XRCC3 geneENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2005Courtney E. Hill Abstract The rapid increase in adenocarcinoma of the lung and mortality amongst women strongly suggests that gender differences exist in sensitivity to certain tobacco carcinogens. In the current study, we performed the mutagen-sensitivity assay, with the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), to test the hypothesis that women are more sensitive to the genotoxic effects of NNK than men. Chromosome aberration (CA) frequencies in peripheral blood lymphocytes (PBLs) from 99 patients were evaluated before and after in vitro exposure to NNK. Because the Thr241Met polymorphism in the DNA-repair gene XRCC3 is associated with increased risk of tobacco-related cancers, especially among women, we also tested the hypothesis that individuals who inherit the homozygous variant 241Met allele are more sensitive to the genotoxic effects of NNK. CA frequency was significantly higher 1 hr after NNK treatment in women, compared with men (P = 0.02). When smoking and gender were considered together, a significant interaction was observed. PBLs from female smokers had significantly higher frequencies of NNK-induced CA, compared with female nonsmokers 1 hr after treatment (P = 0.02). We observed no overall effect of the Thr241Met polymorphism on NNK-induced CA in men, women, smokers, or nonsmokers. Overall, our data indicate that women are more sensitive to the genotoxic effects of NNK than men. Because in past years smoking among women has increased, and in view of the close correlation between NNK exposure and adenocarcinoma of the lung, our data provide a plausible explanation for the recent increase in the incidence of this cancer among women. Environ. Mol. Mutagen., 2005. © 2005 Wiley-Liss, Inc. [source] Differential mutagen sensitivity of peripheral blood lymphocytes from smokers and nonsmokers: Effect of human cytomegalovirus infectionENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3 2004Thomas Albrecht Abstract We used the mutagen sensitivity assay to test the hypothesis that human cytomegalovirus (HCMV) infection modifies the sensitivity of cells to genetic damage from genotoxic agents. Chromosome aberration (CA) frequency in peripheral blood lymphocytes (PBLs) from 20 smokers who were matched with 20 nonsmokers by age (± 5 years), sex, and ethnicity was evaluated following in vitro exposure to bleomycin and/or HCMV infection. Bleomycin induced significant (P < 0.05) concentration-dependent increases in the frequency of aberrant cells, chromatid-type damage (breaks), and chromosome-type aberrations (deletions, rearrangements) in PBLs. The baseline (background) CA frequency was similar in both smokers and nonsmokers. Significantly higher frequencies of aberrant cells (P < 0.05) were observed in PBLs from smokers compared to nonsmokers at all bleomycin concentrations tested (10, 30 and 100 ,g/ml). Infection of PBLs with HCMV induced a significant (P < 0.05) twofold increase in the frequency of CA (primarily chromatid breaks) in PBLs, regardless of the smoking status. PBLs from smokers and nonsmokers infected with HCMV prior to challenge with bleomycin demonstrated significant (P < 0.05) concentration-dependent increases in the levels of aberrant cells, chromatid-type damage (breaks), and chromosome-type aberrations (deletions, rearrangements) compared to noninfected cells challenged with bleomycin. The frequency of induced CA was consistently higher for PBLs derived from smokers relative to nonsmokers (P = 0.06 and 0.002). These data indicate that, individually, both smoking and HCMV infection significantly enhance the sensitivity of PBLs to bleomycin-induced genetic damage. More importantly, the data also suggest that smoking and HCMV infection interact synergistically to enhance the sensitivity of PBLs to such damage. Environ. Mol. Mutagen. 43:169,178, 2004. © 2004 Wiley-Liss, Inc. [source] Chromosome aberrations in peripheral blood lymphocytes of high-risk HPV-infected women with HGSILENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 9 2008Rosa E. Álvarez-Rosero Abstract Genomic instability is one of the main characteristics of malignant tumors, including HPV-induced cervical cancer. The aim of this study was to explore the use of assessing chromosome aberrations (CA) in peripheral blood lymphocytes as a biomarker for genomic instability in high-risk HPV-infected women with high-grade squamous intraepithelial lesions (HGSIL). A total of 120 women were recruited for this study, following cytology/colposcopy evaluation and HPV DNA detection. The study groups consisted of 30 HPV(+) women with histologically confirmed cervical intraepithelial neoplasia grade 2/3 and 30 HPV(+) women with carcinoma in situ (CIS). Two control groups, including 30 women HPV(,) and 30 women HPV(+), were recruited among women who were reported as cytology negative. Lymphocyte cell cultures were established for 52 hr, and 100 complete metaphase cells were evaluated per subject for CA analysis. The results show that women with CIS had significantly higher frequencies of both aneuploidy (0.67 ± 0.20 vs. 0.14 ± 0.08, P = 0.020) and tetraploidy (0.88 ± 0.23 vs. 0.17 ± 0.08, P = 0.013) in comparison with HPV(,) controls. These findings suggest the usefulness of peripheral blood lymphocytes to detect genomic instability associated with HPV-induced HGSIL. Environ. Mol. Mutagen., 2008. © 2008 Wiley-Liss, Inc. [source] Chromosome aberrations in a series of 120 multiple myeloma cases with abnormal karyotypesAMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2007Anwar N. Mohamed We identified 120 multiple myeloma (MM) cases with satisfactory cytogenetic evaluation and abnormal karyotypes. Hyperdiploid karyotype was found in 77 cases (64%), hypodiploid in 30 cases (25%), and the remaining 13 cases (11%) had a pseudodiploid karyotype. The most common numerical abnormalities were gains of chromosomes 15, 9, 3 followed by chromosomes 19, 11, 7, 21, and 5. Whole chromosome losses were also frequent involving primarily chromosomes X/Y, 8, 13, 14, and 22. Most cases showed also structural rearrangements leading to del(1p), dup(1q), del(5q), del(6q), del(8p), del(9p), del(13q), and del(17p). Chromosome 13/13q deletion was found in 52% of cases; complete loss of 13 was observed in 73% of cases, whereas 27% had interstitial deletions. In addition, 13/13q deletions occurred in 75% of nonhyperdiploid myeloma but only 39% of the hyperdiploid had 13/13q deletions. Translocations affecting 14q32/IGH region was seen 40 cases; t(11;14)(q13;q32) in 17 cases, t(14;16)(q32;q23) and t(8;14)(q24;q32) in three cases each, and t(6;14)(p21;q32) and t(1;14)(q21;q32) in two cases each. The remaining 14q32 translocations had various t(V;14) partners or of an undetermined origin. Remarkably, the 14q32/IGH translocations were less frequent in the hyperdiploid karyotypes than the nonhyperdiploid karyotypes (17 vs. 63%). Fourteen cases showed break at 8q24/CMYC site; seven of those had Burkitt's-type translocations. Our results revealed that conventional cytogenetics remains an important tool in elucidating the complex and divers genetic anomalies of MM. Cytogenetics identifies two distinct groups of MM, hyperdiploid and nonhyperdiploid, and establishes the presence of prognostic chromosomal markers such as 13/13q, 17p, 8q24, and 16q aberrations. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source] Searching PubMed for molecular epidemiology studies: The case of chromosome aberrationsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2006Donatella Ugolini Abstract The available tools for searching literature in the field of Molecular Epidemiology are largely unsatisfactory. To identify major problems in retrieving information on this discipline, we comment here on the results of a literature search on cytogenetic biomarkers in children exposed to environmental pollutants. The search, done on the PubMed/MedLine database, was based on a strategy combining descriptors listed in the PubMed Medical Subject Headings (MeSH) Thesaurus and other available tools (free text or phrase search tools). 178 articles were retrieved by searching the period from January 1, 1980 to November 30, 2004. Only 2 of the 178 articles were indexed by the MeSH term "Epidemiology, molecular" (introduced in 1994) and 30 of 178 by the MeSH term "Biological markers" (introduced in 1989). The case of chromosome aberration (CA) was emblematic of the problem: 44 of 78 articles (56.4%) were not pertinent to the search. The reasons for this poor performance are reported and discussed. Authors and indexers may be able to improve the efficiency of article retrieval in the field of molecular epidemiology by using relevant terms in the title and abstract. This may suggest appropriate MeSH terms to the indexers for the indexing process. As regards the difficulty in identifiyng population studies using CA, the introduction of a specific MeSH term for chromosome aberrations when used as a biomarker would improve the search process. Environ. Mol. Mutagen., 2006. © 2006 Wiley-Liss, Inc. [source] Evaluation of biocompatibility of a pectin/polyvinyl alcohol composite hydrogel as a new nucleus materialORTHOPAEDIC SURGERY, Issue 3 2009Nv-zhao Yao MD Objective:, To evaluate the biocompatibility of a new kind of prosthetic nucleus: a pectin/polyvinyl alcohol composite (CoPP) hydrogel. Methods:, According to Chinese national standard GB/-T16886 documents, the toxicity of the CoPP prosthetic nucleus material was examined by cytotoxicity, sensitization, Ames, mice marrow micronucleus, chromosome aberration test of mammalian cell and implantation tests. Results:, Cell growth was similar in the CoPP culture and control groups. No significant difference was found between the CoPP culture and control groups at each time point (P > 0.05). The cell proliferation rate was greater than 100%. In accordance with the relationship between cytotoxicity to proliferation rate, it was confirmed that the cytotoxicity of CoPP was 0 grade. Mice had no allergic reaction when injected with an extract of CoPP. A reverse mutation test with Salmonella typhimurium showed that no significant effect on the number of histidine revertants of TA97, TA98, TA100 and TA102 strains after CoPP was added. The micronucleus rate in bone marrow cells was less than 5%; there was no significant difference compared with the negative control group (P > 0.05). The rate of chromosome aberration was less than 5%; no significant difference was found between the CoPP culture and the control groups. All experimental animal wounds achieved primary healing without exudation, infection or sinus formation. On macroscopic observation, no abscess or hematoma formed at the implantation site. Conclusion:, The CoPP prosthetic nucleus has good biocompatibility and can potentially be used as an implant material. [source] Clonal complex chromosome aberration in non-ossifying fibroma,PEDIATRIC BLOOD & CANCER, Issue 5 2010María Sol Brassesco PhD Abstract Cytogenetic information of non-ossifying fibromas (NOFs) is exceptionally limited. This fact relies, in part, on their benign nature but mainly because most cases evolve undetected or there is no need for surgical intervention. We report the case of a NOF arising in the left tibia of a 14-year-old male with an invariable clonal translocation. The karyotype was denoted as 42,46,XY,t(11;3;14)(q23;p21;p11). There are only two previous reported cases of clonally aberrant NOF. Records from additional cases will be essential to assess whether consistent karyotypic aberrations define this lesion. Pediatr Blood Cancer 2010;54:764,767. © 2010 Wiley-Liss, Inc. [source] Evaluation of genotoxic effects in human peripheral blood leukocytes following an acute in vitro exposure to 900 MHz radiofrequency fieldsBIOELECTROMAGNETICS, Issue 4 2005O. Zeni Abstract Human peripheral blood leukocytes from healthy volunteers have been employed to investigate the induction of genotoxic effects following 2 h exposure to 900 MHz radiofrequency radiation. The GSM signal has been studied at specific absorption rates (SAR) of 0.3 and 1 W/kg. The exposures were carried out in a waveguide system under strictly controlled conditions of both dosimetry and temperature. The same temperature conditions (37.0,±,0.1 °C) were realized in a second waveguide, employed to perform sham exposures. The induction of DNA damage was evaluated in leukocytes by applying the alkaline single cell gel electrophoresis (SCGE)/comet assay, while structural chromosome aberrations and sister chromatid exchanges were evaluated in lymphocytes stimulated with phytohemagglutinin. Alterations in kinetics of cell proliferation were determined by calculating the mitotic index. Positive controls were also provided by using methyl methanesulfonate (MMS) for comet assay and mitomycin-C (MMC), for chromosome aberration, or sister chromatid exchange tests. No statistically significant differences were detected in exposed samples in comparison with sham exposed ones for all the parameters investigated. On the contrary, the positive controls gave a statistically significant increase in DNA damage in all cases, as expected. Thus the results obtained in our experimental conditions do not support the hypothesis that 900 MHz radiofrequency field exposure induces DNA damage in human peripheral blood leukocytes in this range of SAR. Bioelectromagnetics 26:258,265, 2005. © 2005 Wiley-Liss, Inc. [source] Chromosome aberrations in peripheral blood lymphocytes of high-risk HPV-infected women with HGSILENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 9 2008Rosa E. Álvarez-Rosero Abstract Genomic instability is one of the main characteristics of malignant tumors, including HPV-induced cervical cancer. The aim of this study was to explore the use of assessing chromosome aberrations (CA) in peripheral blood lymphocytes as a biomarker for genomic instability in high-risk HPV-infected women with high-grade squamous intraepithelial lesions (HGSIL). A total of 120 women were recruited for this study, following cytology/colposcopy evaluation and HPV DNA detection. The study groups consisted of 30 HPV(+) women with histologically confirmed cervical intraepithelial neoplasia grade 2/3 and 30 HPV(+) women with carcinoma in situ (CIS). Two control groups, including 30 women HPV(,) and 30 women HPV(+), were recruited among women who were reported as cytology negative. Lymphocyte cell cultures were established for 52 hr, and 100 complete metaphase cells were evaluated per subject for CA analysis. The results show that women with CIS had significantly higher frequencies of both aneuploidy (0.67 ± 0.20 vs. 0.14 ± 0.08, P = 0.020) and tetraploidy (0.88 ± 0.23 vs. 0.17 ± 0.08, P = 0.013) in comparison with HPV(,) controls. These findings suggest the usefulness of peripheral blood lymphocytes to detect genomic instability associated with HPV-induced HGSIL. Environ. Mol. Mutagen., 2008. © 2008 Wiley-Liss, Inc. [source] In vitro evaluation of the clastogenicity of fumagillinENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 8 2008Jevrosima Stevanovic Abstract Fumagillin, an antibiotic compound produced by Aspergillus fumigatus, is effective against microsporidia and various Amoeba species, but is also toxic when administered systemically to mammals. Furthermore, a recent in vivo study by Stanimirovic Z et al. 2007: (Mutat Res 628:1,10) indicated genotoxic effects of fumagillin. The aim of the present study was to investigate and explain the clastogenic effects of fumagillin (in the form of fumagillin dicyclohexylamine salt) on human peripheral blood lymphocytes in vitro by sister-chromatid exchanges (SCE), chromosome aberrations (CA), and micronucleus (MN) tests. The mitotic index (MI), proliferation index (PI), and nuclear division index (NDI) were calculated to evaluate the cytotoxic potential of fumagillin. Five concentrations of fumagillin (0.34, 0.68, 1.02, 3.07, and 9.20 ,g/ml) were applied to lymphocyte cultures. All the tested concentrations of fumagillin increased the frequency of SCE per cell significantly (P < 0.001 or P < 0.01) compared with the negative control. A significant (P < 0.001) increase in frequency of structural CA was observed at the three highest concentrations in comparison with the negative control. In addition, the three highest test concentrations increased MN formation and decreased MI, PI, and NDI significantly compared with the negative control. The present results indicate that fumagillin is clastogenic and cytotoxic to cultured human lymphocytes. Environ. Mol. Mutagen., 2008. © 2008 Wiley-Liss, Inc. [source] In vivo genotoxic effects of industrial waste leachates in mice following oral exposureENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 5 2006Saurabh Chandra Abstract Contamination of ground water by industrial waste poses potential health hazards for man and his environment. The improper disposal of toxic wastes could allow genotoxic chemicals to percolate into ground waters, and these contaminated ground waters may produce toxicity, including mutation and eventually cancer, in exposed individuals. In the present study, we evaluated the in vivo genotoxic potential of leachates made from three different kinds of industrial waste (tannery waste, metal-based waste, and waste containing dyes and pigments) that are disposed of in areas adjoining human habitation. Three different doses of test leachates were administered by oral gavage for 15 consecutive days to Swiss albino mice; their bone marrow cells were examined for chromosome aberrations (CAs), micronucleated polychromatic erythrocytes (MNPCEs), and DNA damage using the alkaline Comet assay. Exposure to the leachates resulted in significant (P < 0.05 or P < 0.001) dose-dependent increases in chromosome and DNA damage. Fragmented chromosomes and chromatid breaks were the major CAs observed. Chemical analysis of the leachates indicated that chromium and nickel were elevated above the limits established by health organizations. The highest levels of genotoxicity were produced by the metal-based leachate and the tannery-waste leachate, while the dye-waste leachate produced weaker genotoxic responses. The cytogenetic abnormalities and DNA damage produced by the leachates indicate that humans consuming water contaminated with these materials are at increased risk of developing adverse health consequences. Environ. Mol. Mutagen., 2006. © 2006 Wiley-Liss, Inc. [source] Searching PubMed for molecular epidemiology studies: The case of chromosome aberrationsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2006Donatella Ugolini Abstract The available tools for searching literature in the field of Molecular Epidemiology are largely unsatisfactory. To identify major problems in retrieving information on this discipline, we comment here on the results of a literature search on cytogenetic biomarkers in children exposed to environmental pollutants. The search, done on the PubMed/MedLine database, was based on a strategy combining descriptors listed in the PubMed Medical Subject Headings (MeSH) Thesaurus and other available tools (free text or phrase search tools). 178 articles were retrieved by searching the period from January 1, 1980 to November 30, 2004. Only 2 of the 178 articles were indexed by the MeSH term "Epidemiology, molecular" (introduced in 1994) and 30 of 178 by the MeSH term "Biological markers" (introduced in 1989). The case of chromosome aberration (CA) was emblematic of the problem: 44 of 78 articles (56.4%) were not pertinent to the search. The reasons for this poor performance are reported and discussed. Authors and indexers may be able to improve the efficiency of article retrieval in the field of molecular epidemiology by using relevant terms in the title and abstract. This may suggest appropriate MeSH terms to the indexers for the indexing process. As regards the difficulty in identifiyng population studies using CA, the introduction of a specific MeSH term for chromosome aberrations when used as a biomarker would improve the search process. Environ. Mol. Mutagen., 2006. © 2006 Wiley-Liss, Inc. [source] Nickel potentiates the genotoxic effect of benzo[a]pyrene in Chinese hamster lung V79 cellsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3 2006Cheng Z. Deng Abstract The modulating effect of acute exposure to NiCl2 on the induction of chromosome aberrations by a model carcinogen, benzo[a]pyrene (B[a]P), was examined in Chinese hamster V79 lung cells. At concentrations up to 20 ,g/ml (84.2 ,M), NiCl2 did not significantly increase the frequency of chromosome aberrations in V79 cells when the cells were exposed concomitantly to 0.5 ,g/ml B[a]P. Addition of the S15 liver microsomal fraction together with the B[a]P did not alter the results. Addition of NiCl2 2 hr before treatment of cells with 0.5 ,g/ml B[a]P also did not result in a significant elevation of the frequency of chromosome aberrations, even at NiCl2 concentrations as high as 20 ,g/ml. Contrasting sharply with these findings, when V79 cells were treated with NiCl2 immediately after B[a]P exposure, a significant increase in the frequency of chromosome damage was observed at NiCl2 concentrations as low as 5 ,g/ml (21.1 ,M). NiCl2 -mediated enhancement of chromosome damage was also observed when V79 cells were exposed to the reactive B[a]P intermediate, benzo[a]pyrene,r,7,t,8-dihydrodiol- t,9,10-epoxide (BPDE). In the BPDE-treated cells, the level of NiCl2 -mediated enhancement was similar to that observed with the tumor promoter 12- o -tetradecanoylphorbol-13-acetate (TPA, 100 ng/ml). These results are consistent with the view that the effect of nickel (II) on B[a]P-induced genetic damage is dependent on the relative times of exposure to Ni2+ and B[a]P. NiCl2 did not enhance the frequency of chromosome aberrations induced by Chromium (VI), regardless of the order of addition of the chemicals to the V79 cells. These results suggest that nickel may act as a promoter of chemically-induced genetic damage through induction of error-prone repair. Environ. Mol. Mutagen., 2006. © 2005 Wiley-Liss, Inc. [source] Aluminum induces chromosome aberrations, micronuclei, and cell cycle dysfunction in root cells of Vicia fabaENVIRONMENTAL TOXICOLOGY, Issue 2 2010Min Yi Abstract Aluminum (Al) exists naturally in air, water, and soil, and also in our diet. Al can be absorbed into the human body and accumulates in different tissues, which has been linked to the occurrence of Alzheimer's disease and various neurological disorders. By using Vicia cytogenetic tests, which are commonly used to monitor the genotoxicity of environmental pollutants, cytogenetic effects of aluminum (AlCl3) were investigated in this study. Present results showed that Al caused significant increases in the frequencies of micronuclei (MN) and anaphase chromosome aberrations in Vicia faba root tips exposed to Al over a concentration-tested range of 0.01,10 mM for 12 h. The frequency of micronucleated cells was higher in Al-treated groups at pH 4.5 than that at pH 5.8. Similarly, AlCl3 treatment caused a decrease in the number of mitotic cells in a dose- and pH-dependent manner. The number of cells in each mitotic phase changed in Al-treated samples. Mitotic indices (MI) decreased with the increases of pycnotic cells. Our results demonstrate that aluminum chloride is a clear clastogenic/genotoxic and cytotoxic agent in Vicia root cells. The V. faba cytogenetic test could be used for the genotoxicity monitoring of aluminum water contamination. © 2009 Wiley Periodicals, Inc. Environ Toxicol, 2010. [source] microRNAs in acute myeloid leukemia: Expression patterns, correlations with genetic and clinical parameters, and prognostic significanceGENES, CHROMOSOMES AND CANCER, Issue 3 2010Rotraud Wieser Acute myeloid leukemia (AML) is a malignant disease of hematopoietic cells whose emergence, course, and prognosis is affected by specific recurrent genetic alterations like chromosome aberrations and point mutations, as well as by changes in the expression of certain genes. In the past 2 years, microRNAs (miRNAs),a novel class of small RNA molecules involved in posttranscriptional gene regulation,have also been shown to be aberrantly expressed in AML. Furthermore, specific miRNA expression patterns were found to be associated with certain genetic and cytogenetic alterations in this disease, and two studies identified miRNAs whose expression levels were predictive of survival. Interestingly, the results of these analyses showed only very limited congruence. This review summarizes published reports on the expression patterns of miRNAs in AML, and discusses possible reasons for the differences in their results. © 2009 Wiley-Liss, Inc. [source] Definitive molecular cytogenetic characterization of 15 colorectal cancer cell lines,GENES, CHROMOSOMES AND CANCER, Issue 3 2010Turid Knutsen In defining the genetic profiles in cancer, cytogenetically aberrant cell lines derived from primary tumors are important tools for the study of carcinogenesis. Here, we present the results of a comprehensive investigation of 15 established colorectal cancer cell lines using spectral karyotyping (SKY), fluorescence in situ hybridization, and comparative genomic hybridization (CGH). Detailed karyotypic analysis by SKY on five of the lines (P53HCT116, T84, NCI-H508, NCI-H716, and SK-CO-1) is described here for the first time. The five lines with karyotypes in the diploid range and that are characterized by defects in DNA mismatch repair had a mean of 4.8 chromosomal abnormalities per line, whereas the 10 aneuploid lines exhibited complex karyotypes and a mean of 30 chromosomal abnormalities. Of the 150 clonal translocations, only eight were balanced and none were recurrent among the lines. We also reviewed the karyotypes of 345 cases of adenocarcinoma of the large intestine listed in the Mitelman Database of Chromosome Aberrations in Cancer. The types of abnormalities observed in the cell lines reflected those seen in primary tumors: there were no recurrent translocations in either tumors or cell lines; isochromosomes were the most common recurrent abnormalities; and breakpoints occurred most frequently at the centromeric/pericentromeric and telomere regions. Of the genomic imbalances detected by array CGH, 87% correlated with chromosome aberrations observed in the SKY studies. The fact that chromosome abnormalities predominantly result in copy number changes rather than specific chromosome or gene fusions suggests that this may be the major mechanism leading to carcinogenesis in colorectal cancer. Published 2009 Wiley-Liss, Inc. [source] Characterization of t(6;11)(p21;q12) in a renal-cell carcinoma of an adult patientGENES, CHROMOSOMES AND CANCER, Issue 5 2007Lorenza Pecciarini Renal-cell carcinoma (RCC) constitutes a heterogeneous group of tumors with specific chromosome aberrations. Recently, a new small group of RCC, occurring in children and young adults, has been described as characterized by t(6;11)(p21;q12). It has been shown that this translocation results in the fusion of the 5, portion of the ALPHA gene (11q12) with the transcription factor gene TFEB (6p21). Herewith, we report the first complete cytogenetic and molecular characterization of a t(6;11)-positive RCC of an adult patient, a 54-year-old woman. The tumor was histologically defined as RCC with peculiar features and it was negative for epithelial markers and positive for melanocytic markers. Chromosome QFQ banding analysis of short-term cultured cells from the RCC showed t(6;11)(p21;q12) as the sole cytogenetic abnormality. The translocation was confirmed by FISH analysis. RT-PCR analysis, performed on total RNA isolated from both neoplastic and normal tissue samples, revealed an ALPHA,TFEB chimeric transcript in the tumor sample; sequencing of the RT-PCR product defined a novel TFEB gene breakpoint cluster region, broader than the one reported thus far. Western blot analysis showed a band at the expected size of wild-type TFEB in the neoplastic tissue compared to the normal sample, supporting that the fusion gene does not encode for a chimeric protein but it causes an upregulation of the wild-type TFEB. Our data contribute to define better this rare RCC type, which is typical not only of childhood but can also be found in adulthood. © 2007 Wiley-Liss, Inc. [source] Identification of NUP98 abnormalities in acute leukemia: JARID1A (12p13) as a new partner geneGENES, CHROMOSOMES AND CANCER, Issue 5 2006Laura J. C. M. van Zutven Chromosome rearrangements are found in many acute leukemias. As a result, genes at the breakpoints can be disrupted, forming fusion genes. One of the genes involved in several chromosome aberrations in hematological malignancies is NUP98 (11p15). As NUP98 is close to the 11p telomere, small translocations might easily be missed. Using a NUP98 -specific split-signal fluorescence in situ hybridization (FISH) probe combination, we analyzed 84 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia, or myelodysplastic syndrome with either normal karyotypes or 11p abnormalities to investigate whether there are unidentified 11p15 rearrangements. Neither NUP98 translocations nor deletions were identified in cases with normal karyotypes, indicating these aberrations may be very rare in this group. However, NUP98 deletions were observed in four cases with unbalanced 11p aberrations, indicating that the breakpoint is centromeric of NUP98. Rearrangements of NUP98 were identified in two patients, both showing 11p abnormalities in the diagnostic karyotype: a t(4;11)(q1?3;p15) with expression of the NUP98,RAP1GDS1 fusion product detected in a 60-year-old woman with AML-M0, and an add(11)(p15) with a der(21)t(11;21)(p15;p13) observed cytogenetically in a 1-year-old boy with AML-M7. JARID1A was identified as the fusion partner of NUP98 using 3, RACE, RT-PCR, and FISH. JARID1A, at 12p13, codes for retinoblastoma binding protein 2, a protein implicated in transcriptional regulation. This is the first report of JARID1A as a partner gene in leukemia. © 2006 Wiley-Liss, Inc. [source] Complex chromosome aberrations persist in individuals many years after occupational exposure to densely ionizing radiation: An mFISH studyGENES, CHROMOSOMES AND CANCER, Issue 1 2005M. Prakash Hande Long-lived, sensitive, and specific biomarkers of particular mutagenic agents are much sought after and potentially have broad applications in the fields of cancer biology, epidemiology, and prevention. Many clastogens induce a spectrum of chromosome aberrations, and some of them can be exploited as biomarkers of exposure. Densely ionizing radiation, for example, alpha particle radiation (from radon or plutonium) and neutron radiation, preferentially induces complex chromosome aberrations, which can be detected by the 24-color multifluor fluorescence in situ hybridization (mFISH) technique. We report the detection and quantification of stable complex chromosome aberrations in lymphocytes of healthy former nuclear-weapons workers, who were exposed many years ago to plutonium, gamma rays, or both, at the Mayak weapons complex in Russia. We analyzed peripheral-blood lymphocytes from these individuals for the presence of persistent complex chromosome aberrations. A significantly elevated frequency of complex chromosome translocations was detected in the highly exposed plutonium workers but not in the group exposed only to high doses of gamma radiation. No such differences were found for simple chromosomal aberrations. The results suggest that stable complex chromosomal translocations represent a long-lived, quantitative, low-background biomarker of densely ionizing radiation for human populations exposed many years ago. © 2005 Wiley-Liss, Inc. [source] Genomic imbalances in CML blast crisis: 8q24.12,q24.13 Segment identified as a common region of over-representationGENES, CHROMOSOMES AND CANCER, Issue 4 2003Susan M. Gribble The acute phase of chronic myeloid leukemia (CML) is accompanied by secondary chromosomal changes. The additional changes have a non-random pattern; however, highly abnormal (marker) chromosomes are reported in some 20% of abnormal karyotypes. These marker chromosomes have proved to be beyond the resolution of conventional G-banding analysis. We used molecular cytogenetic techniques to determine the structure of complex chromosome markers in 10 CML-derived cell lines after our investigations of CML patients in blast crisis. Multicolor fluorescence in situ hybridization identified a multitude of structural chromosome aberrations. In addition, genomic gains identified by comparative genomic hybridization (CGH) were mapped to highly complex marker chromosomes in more than one cell line. The most common genomic loss detected by CGH affected chromosome 9, whereas the most common genomic gains affected, in order of frequency, the sequences of 8q, 6, and 13q. The smallest discrete amplification on 8q was identified in cell line MEG-01. This amplicon contains sequences represented by the marker D8S263/RMC08P029 but did not contain the proximal MYC gene or a more distal marker, D8S256/RMC08P025. We determined the size of the amplicon to be less than the chromosome segment 8q24.12,q24.13. The use of region- and locus-specific probes to analyze the organization of highly complex marker structures aided the identification of preferentially amplified genomic regions. The resultant amplifications could harbor gene(s) driving disease progression. © 2003 Wiley-Liss, Inc. [source] International workshop on the relationship of prior therapy to balanced chromosome aberrations in therapy-related myelodysplastic syndromes and acute leukemia: Overview reportGENES, CHROMOSOMES AND CANCER, Issue 4 2002Janet D. Rowley First page of article [source] Genotoxicity study in lymphocytes of offset printing workersJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2006Hüseyin Aksoy Abstract The potential cytogenetic damage in offset printing workers was evaluated using sister chromatid exchanges (SCEs), chromosome aberrations (CAs) and micronuclei (MN) as biomarkers in peripheral lymphocytes of 26 volunteers (14 workers, 12 controls). The CA, SCE and MN frequency of offset printing workers was significantly higher than in their controls. The replication index (RI) was not affected while the mitotic index (MI) was affected most in the workers. It can be concluded from this study that chronic occupational exposure to printing dyes and thinner may lead to a slightly increased risk of genetic damage among offset printing workers. Copyright © 2005 John Wiley & Sons, Ltd. [source] Association between TP53 gene ARG72PRO polymorphism and chromosome aberrations in human cancersMOLECULAR CARCINOGENESIS, Issue 6 2010Nicolay V. Litviakov Abstract It is well known that the TP53 gene considerably influences on DNA repair processes. Polymorphisms in the TP53 gene, particularly the well-known Arg72Pro in codon 72 of exon 4 (Ex4+119 G>C; rs1042522), can modify the functionality of the p53 protein and activation of DNA repair. Actually, polymorphic variants Arg and Pro were found to have different properties of regulation of TP53-dependent DNA repair target genes, that can effect various levels of chromosome aberrations in cancer patients with these genotypes. Here, we studied frequency of chromatid breaks (CB), chromosome-type aberrations (CTA) and aberrant cells (AC) in cancer patients (n,=,102) with various Arg72Pro genotypes. It was shown that the Arg variant of TP53 gene is associated with high frequency of AC and chromatid breaks. That is Arg/Arg carriers have more different chromosome aberrations in comparison to individuals with Arg/Pro and Pro/Pro genotypes (P,<,0.05). Conversely, the lowest level of AC and chromatid breaks were detected in cancer patients with the Pro/Pro genotype. A completely unexpected result was that women with Arg/Arg genotype had the most high frequency of CB and AC in comparison to Arg/Pro and Pro/Pro women carriers (P,<,0.001). In the group of male patients we did not show any differences in chromosome aberrations between carriers of Arg72Pro genotypes. In conclusion, the TP53 gene Arg72Pro polymorphism appreciably influence on occurrence of chromosome aberrations in cancer. Mol. Carcinog. © 2010 Wiley-Liss, Inc. [source] Monochorionic-diamniotic twins discordant in gender from a naturally conceived pregnancy through postzygotic sex chromosome loss in a 47,XXY zygotePRENATAL DIAGNOSIS, Issue 8 2008Nicolas H. Zech Abstract Objective It is generally believed that monochorionic-diamniotic twin pregnancies result from one fertilized oocyte with both siblings having the same genotype and phenotype. In rare instances, due to somatic mutations or chromosome aberrations, the karyotypes and phenotypes of the two twins can differ. Method We report cytogenetic, molecular genetic and clinical examinations in monochorionic-diamniotic twins discordant in gender. Results The monochorionic-diamniotic status of the twins was diagnosed by ultrasound and histologic examination of the placenta. Prenatal chromosome examination performed on amniocytes revealed a normal female karyotype in one and a 46,XX(26)/46,XY(3) karyotype in the other twin. Molecular examinations confirmed monozygosity despite discordant sex. Based on the cytogenetic and molecular results of lymphocytes and placental cells, the only explanation for gender discordance was that the conceptus originally had a 47,XXY chromosome complement. Conclusion A 47,XXY zygote appears to have undergone a twinning process. A postzygotic loss of the X chromosome in some cells and the Y chromosome in other cells, either before or after twinning, resulted in 46,XX/46,XY mosaicism in both monozygotic (MZ) twins. The sex discordance of the MZ twins can be explained by different proportions of the 46,XX and 46,XY cell lines in the gonads and other tissues. Copyright © 2008 John Wiley & Sons, Ltd. [source] Detection of chromosome aberrations during prenatal genetic testing for single gene disordersPRENATAL DIAGNOSIS, Issue 7 2005Joël Zlotogora No abstract is available for this article. [source] Prenatal diagnosis and molecular cytogenetic analysis of partial monosomy 10q (10q25.3,qter) and partial trisomy 18q (18q23,qter) in a fetus associated with cystic hygroma and ambiguous genitaliaPRENATAL DIAGNOSIS, Issue 6 2005Chih-Ping Chen Abstract Objectives To present the prenatal diagnosis and molecular cytogenetic analysis of a fetus with nuchal cystic hygroma and ambiguous genitalia. Case and Methods Amniocentesis was performed at 16 weeks' gestation because of the abnormal fetal sonographic finding of a large septated nuchal cystic hygroma. Genetic amniocentesis revealed a terminal deletion in the long arm of chromosome 10. The paternal karyotype was subsequently found to be 46,XY,t(10;18)(q25.3;q23). The maternal karyotype was normal. The pregnancy was terminated. A hydropic fetus was delivered with a septated nuchal cystic hygroma and ambiguous genitalia. Fluorescence in situ hybridization (FISH), microarray-based comparative genomic hybridization (CGH), and polymorphic DNA markers were used to investigate the involved chromosomal segments. Results FISH study showed absence of the 10q telomeric probe and presence of the 18q telomeric probe in the derivative chromosome 10. Microarray-based CGH analysis showed loss of distal 10q and gain of distal 18q. Polymorphic DNA marker analysis determined the breakpoints. The fetal karyotype was 46,XY,der(10)t(10;18)(q25.3;q23)pat. The chromosome aberration resulted in partial monosomy 10q (10q25.3,qter) and partial trisomy 18q (18q23,qter). Conclusions The present case provides evidence that partial monosomy 10q (10q25.3,qter) with partial trisomy 18q (18q23,qter) can be a genetic cause of fetal cystic hygroma and ambiguous genitalia. Cytogenetic analysis for prenatally detected structural abnormalities may detect unexpected inherited chromosome aberrations. Copyright © 2005 John Wiley & Sons, Ltd. [source] Evaluation of genotoxic effects in human peripheral blood leukocytes following an acute in vitro exposure to 900 MHz radiofrequency fieldsBIOELECTROMAGNETICS, Issue 4 2005O. Zeni Abstract Human peripheral blood leukocytes from healthy volunteers have been employed to investigate the induction of genotoxic effects following 2 h exposure to 900 MHz radiofrequency radiation. The GSM signal has been studied at specific absorption rates (SAR) of 0.3 and 1 W/kg. The exposures were carried out in a waveguide system under strictly controlled conditions of both dosimetry and temperature. The same temperature conditions (37.0,±,0.1 °C) were realized in a second waveguide, employed to perform sham exposures. The induction of DNA damage was evaluated in leukocytes by applying the alkaline single cell gel electrophoresis (SCGE)/comet assay, while structural chromosome aberrations and sister chromatid exchanges were evaluated in lymphocytes stimulated with phytohemagglutinin. Alterations in kinetics of cell proliferation were determined by calculating the mitotic index. Positive controls were also provided by using methyl methanesulfonate (MMS) for comet assay and mitomycin-C (MMC), for chromosome aberration, or sister chromatid exchange tests. No statistically significant differences were detected in exposed samples in comparison with sham exposed ones for all the parameters investigated. On the contrary, the positive controls gave a statistically significant increase in DNA damage in all cases, as expected. Thus the results obtained in our experimental conditions do not support the hypothesis that 900 MHz radiofrequency field exposure induces DNA damage in human peripheral blood leukocytes in this range of SAR. Bioelectromagnetics 26:258,265, 2005. © 2005 Wiley-Liss, Inc. [source] Radiofrequency exposure and mammalian cell toxicity, genotoxicity, and transformationBIOELECTROMAGNETICS, Issue S6 2003Martin L. Meltz Abstract The published in vitro literature relevant to the issue of the possible induction of toxicity, genotoxicity, and transformation of mammalian cells due to radiofrequency field (RF) exposure is examined. In some instances, information about related in vivo studies is presented. The review is from the perspective of technical merit and also biological consistency, especially with regard to those publications reporting a positive effect. The weight of evidence available indicates that, for a variety of frequencies and modulations with both short and long exposure times, at exposure levels that do not (or in some instances do) heat the biological sample such that there is a measurable increase in temperature, RF exposure does not induce (a) DNA strand breaks, (b) chromosome aberrations, (c) sister chromatid exchanges (SCEs), (d) DNA repair synthesis, (e) phenotypic mutation, or (f) transformation (cancer-like changes). While there is limited experimental evidence that RF exposure induces micronuclei formation, there is abundant evidence that it does not. There is some evidence that RF exposure does not induce DNA excision repair, suggesting the absence of base damage. There is also evidence that RF exposure does not inhibit excision repair after the induction of thymine dimers by UV exposure, as well as evidence that indicates that RF is not a co-carcinogen or a tumor promoter. The article is in part a tutorial, so that the reader can consider similarities and discrepancies between reports of RF-induced effects relative to one another. Bioelectromagnetics Supplement 6:S196,S213, 2003. © 2003 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||