• Title/Summary/Keyword: Chromosome aberrations

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Chromosome Imbalances and Alterations of AURKA and MYCN Genes in Children with Neuroblastoma

  • Inandiklioglu, Nihal;Yilmaz, Sema;Demirhan, Osman;Erdogan, seyda;Tanyeli, Atila
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5391-5397
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    • 2012
  • Background: Neuroblastoma (NB), like most human cancers, is characterized by genomic instability, manifested at the chromosomal level as allelic gain, loss or rearrangement. Genetics methods, as well as conventional and molecular cytogenetics may provide valuable clues for the identification of target loci and successful search for major genes in neuroblastoma. We aimed to investigate AURKA and MYCN gene rearrangements and the chromosomal aberrations (CAs) to determine the prognosis of neuroblastoma. Methods: We performed cytogenetic analysis by G-banding in 25 cases [11 girls (44%) and 14 boys (66%)] and in 25 controls. Fluorescence in situ hybridization (FISH) with AURKA and MYCN gene probes was also used on interphase nuclei to screen for alterations. Results: Some 18.4% of patient cells exhibited CAs., with a significant difference between patient and control groups in the frequencies (P<0.0001). Some 72% of the cells had structural aberrations, and only 28% had numerical chnages in patients. Structural aberrations consisted of deletions, translocations, breaks and fragility in various chromosomes, 84% and 52% of the patients having deletions and translocations, respectively. Among these expressed CAs, there was a higher frequency at 1q21, 1q32, 2q21, 2q31, 2p24, 4q31, 9q11, 9q22, 13q14, 14q11.2, 14q24, and 15q22 in patients. 32% of the patients had chromosome breaks, most frequently in chromosomes 1, 2, 3, 4, 5, 8, 9, 11, 12, 19 and X. The number of cells with breaks and the genomic damage frequencies were higher in patients (p<0.001). Aneuploidies in chromosomes X, 22, 3, 17 and 18 were most frequently observed. Numerical chromosome abnormalities were distinctive in 10.7% of sex chromosomes. Fragile sites were observed in 16% of our patients. Conclusion: Our data confirmed that there is a close correlation between amplification of the two genes, amplification of MYCN possibly contributing significantly to the oncogenic properties of AURKA. The high frequencies of chromosomal aberrations and amplifications of AURKA and MYCN genes indicate prognostic value in children with neuroblastomas and may point to contributing factors in their development.

Ploidy Characteristics of NS-1 Cells Resistant to BCNU or CCNU and Immune mediated Cytotoxicity in vitro (항암제와 세포독성에 내성을 나타내는 생쥐 임파종 세포(NS-1)의 염색체 분포특성)

  • Shim, Woo-Nam;Kim, Young-Min;Kim, Joo-Deuk;Lee, Won-Young
    • The Journal of the Korean Society for Microbiology
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    • v.19 no.1
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    • pp.85-108
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    • 1984
  • In order to study the relationship between resistance of tumor cells to anticancer drugs and immunologic cytotoxicity and their chromosome number, a line of cancer cells (NS-1) was exposed to BCNU and CCNU in vitro. Characteristics of the distribution of chromosome number of the survived cells were then comparatively analyzed. Effect of immune mediated cytotoxicity, i.e. complement and cell-mediated cytotoxicity, on the ploidy characteristics was observed in the same way. NS-1 cells were found to be a population of neoplastic cells of heterogeneity having 5 to 115 chromosomes per cell in metaphase. The majority of the cells were belong to the class of chromosome number 56 to 60 which were considered as the stem cell line. Dramatic changes in the distribution of chromosome number following drug treatment were not observed. However the range of chromosome distribution was slightly changed. Characteristics of chromosomal distribution of drug treated cells were not significantly varied by different doses of drug treated. Changed chromosomal distribution patterns of drug treated cells were reversible, especially the cells having 56 to 60 chromosomes recovered rapidly. Cells having 41-60 and 61-80 chromosomes among cells treated with BCNU and cells with 41-60 chromosomes after CCNU treatment were the major population which regenerated continuously. Following BCNU treatment cells having 61-80 chromosomes were not varied much whereas CCNU treatment affects the population in the same class. Chromosomal aberrations were significantly enhanced by BCNU and CCNU treatment. The frequency of chromosomal aberrations was greater in cells having more than 40 chromosomes compared with that in cells having less than 40 chromosomes. Changes in ploidy characteristics of the cells following complement mediated and cell mediated cytotoxicity were not significant. Therefore it was tentatively concluded that association of numerical distribution pattern of NS-1 cells with the response to the treatment used in this experiment was not recognized.

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Effects of gamma-irradiation on the infectivity and chromosome aberration of Clonorchis sinensis

  • Park, Gab-Man;Yong, Tai-Soon
    • Parasites, Hosts and Diseases
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    • v.41 no.1
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    • pp.41-45
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    • 2003
  • Effects of gamma irradiation on the worm survival and chromosomal aberration of Clonorchis sinensis were studied. The metacercariae irradiated with various amounts of gamma radiation (ranging from 5 Gy to 50 Gy) were fed to rats, and the effects were compared with those of non-irradiated controls. Recovery rates of adult worms in irradiated groups were reduced gradually as increasing of the irradiation doses. No worm was recovered from rats which were fed with 50 Gy irradiated metacercariae. The chromosome number was 2n = 56 in all worms from all experimental groups. However, the groups irradiated with 20 Gy, 25 Gy or 30 Gy showed variations in the chromosome number, depending on different cells in the same individual. Radiation doses used in this study did not appear to induce chromosome aberrations, however, irradiation with 30 Gy showed slightly reduced chromosome size.

Mechanism of Arsenic-Induced Cytotoxiciht in CHO Cells (CHO 세포에서 비소의 세포독성기전)

  • 정해원;기혜성;박영철;한정호;유일재
    • Environmental Mutagens and Carcinogens
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    • v.16 no.2
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    • pp.117-123
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    • 1996
  • This study was carried out to examine the mechanism of Arsenic cytotoxicity through several in vitro test systems. Dose-dependent decrease of cell survival by Arsenic was observed by colony forming assay. Arsenic was weak mutagenic in inducing HGPRT point mutation in CHO cells. The frequency of chromosomal aberrations increased in a dose-dependent manner and the most frequent type of chromosomal aberrations induced by Arsenic were chromatid type deletions. U!trafiltrates of culture media from CHO cells treated with Arsenic induced sister chromatid exchanges(SCE) in CHO cells and Arsenic was able to induce lipid peroxidation in CHO cells. The results suggested that the ultrafiltrates of media from CHO cells treated with Arsenic contain clastogenic factor(CF) and Iipid peroxidation might be involved in the formation of CF.

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Nuclear Anomalies, Chromosomal Aberrations and Proliferation Rates in Cultured Lymphocytes of Head and Neck Cancer Patients

  • George, Alex;Dey, Rupraj;Bhuria, Vikas;Banerjee, Shouvik;Ethirajan, Sivakumar;Siluvaimuthu, Ashok;Saraswathy, Radha
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1119-1123
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    • 2014
  • Head and neck cancers (HNC) are extremely complex disease types and it is likely that chromosomal instability is involved in the genetic mechanisms of its genesis. However, there is little information regarding the background levels of chromosome instability in these patients. In this pilot study, we examined spontaneous chromosome instability in short-term lymphocyte cultures (72 hours) from 72 study subjects - 36 newly diagnosed HNC squamous cell carcinoma patients and 36 healthy ethnic controls. We estimated chromosome instability (CIN) using chromosomal aberration (CA) analysis and nuclear level anomalies using the Cytokinesis Block Micronucleus Cytome Assay (CBMN Cyt Assay). The proliferation rates in cultures of peripheral blood lymphocytes (PBL) were assessed by calculating the Cytokinesis Block Proliferation Index (CBPI). Our results showed a significantly higher mean level of spontaneous chromosome type aberrations (CSAs), chromatid type aberration (CTAs) dicentric chromosomes (DIC) and chromosome aneuploidy (CANE UP) in patients (CSAs, $0.0294{\pm}0.0038$; CTAs, $0.0925{\pm}0.0060$; DICs, $0.0213{\pm}0.0003$; and CANE UPs, $0.0308{\pm}0.0035$) compared to controls (CSAs, $0.0005{\pm}0.0003$; CTAs, $0.0058{\pm}0.0015$; DICs, $0.0005{\pm}0.0003$; and CANEUPs, $0.0052{\pm}0.0013$) where p<0.001l. Similarly, spontaneous nuclear anomalies showed significantly higher mean level of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) among cases (MNi, $0.01867{\pm}0.00108$; NPBs, $0.0156{\pm}0.00234$; NBUDs, $0.00658{\pm}0.00068$) compared with controls (MNi, $0.00027{\pm}0.00009$; NPBs, $0.00002{\pm}0.00002$; NBUDs, $0.00011{\pm}0.00007$).The evaluation of CBPI supported genomic instability in the peripheral blood lymphocytes showing a significantly lower proliferation rate in HNC patients ($1.525{\pm}0.005552$) compared to healthy subjects ($1.686{\pm}0.009520$) (p<0.0001). In conclusion, our preliminary results showed that visible spontaneous genomic instability and low rate proliferation in the cultured peripheral lymphocytes of solid tumors could be biomarkers to predict malignancy in early stages.

Genotoxicily Studies of An Anticancer Agent of Camptothecin Series, CKD-602 (Camptothecin계 항암제 CKD-602의 유전독성평가)

  • 하광원;오혜영;허옥순;박장환;손수정;한의식;김종원;강일현;강혁준
    • Environmental Mutagens and Carcinogens
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    • v.18 no.2
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    • pp.129-134
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    • 1998
  • To evaluate the genotoxicity of CKD-602, an anticancer agent the in viかo reverse mutation assay using Salmonella typhimurium, the Chromosome aberration assay using Chinese hamster lung (CHL) cells and the in vivo micronucleus assay using bone marrow cells of ddY mice were performed. In the reverse mutation assay, CKD-602 did not induced mutagenicity in Salmonella typhimurium TA 98, TA 100, TA 1535, and TA 1537 strains with and without metabolic activation. In the chromosome aberration test using CHL cells, there was an increased incidence of structural aberrations induced by CKD-602 without metabolic activation during 24 and 48 hours, but CKD-602 did not induce chromosome aberration with metabolic activation. The in vivo induction of micronuclei was measured in polychromatic erythrocytes of bone marrow of male ddY mice. At 24 hours after treatment with CED-602 by i.p. once, there was an increased incidence of micronucleated polychromatic erythrocytes in bone marrow of ddY male mice.

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Effects of absorbed radioactive sulfur (S35) in plant cell. I. Mitotic chromosome aberrations in rye seedling induced by the treatment of S35 solution (식물에 미치는 방사성 동위원소 S35의 영향에 대하여 (제1보) 호밀 근단세포의 염색체 이상수발에 관한 연구)

  • 홍순우
    • Journal of Plant Biology
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    • v.8 no.1_2
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    • pp.1-4
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    • 1965
  • Beta-ray irradiation effects on structural changes of the chromosomes in root tip of rye, Secale cereale L., seedlings, particularly the frequency of chromosome bridge induction at anaphase stage treated with radioactive sulfur (S35) solutions were studied in this experiment. Among the four different concentrations of isotope solution, the lowest one, 0.4$\mu$c solution, has shown weak effect on the induction of chromosome aberration. On the other hand, higher concentration, 25.6$\mu$c solution, induced higher frequency of chromosome bridge induction as much as 4.3%. Concerning the relationship between the ages of after treatment and the ranges of concentration, the higher concentrations showed more pronounced effects than the lower ones.

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Chromosome Aberration and Sister Chromatid Exchange for the Assessment of Cadmium Toxicity (카드뮴독성을 평가하기 위한 방법으로서의 염색체 이상 및 자매염색체 교환)

  • 맹승희;정해원
    • Journal of Environmental Health Sciences
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    • v.17 no.1
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    • pp.110-119
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    • 1991
  • This study was performed to investigate the applicability of 9 chromosome aberration and sister chromatid exchange analysis for the assessment of cytotoxicity and cytogenetic effects of cadmium. Induction of chromosome aberration and sister chromatid exchange in CHO-K1 cells and human peripheral lymphocytes by 2 hour-treatment of CdCl$_{2}$ with various concentrations was observed in relation to their frequencies and types of aberration. The frequency of chromosome aberration in CHO cells treated with CdCl$+{2}$ at G$_{1}$ was increased with dose-dependent manner. When human peripheral lymphocytes were treated with cadmium at G0 and harvested at 72 hours there after, the response was dose-dependent and all the aberrations were also chromatid types. There was no significant increase in frequencies of sister chromatid exchange in both CHO cells and human lymphocytes treated with different concentrations of cadmium. It was suggested that SCE analysis was not a good assessment method for cadmium toxicity.

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