Spontaneous chromosomal aberrations in Fanconi anaemia,ataxia telangiectasia fibroblast and Bloom's syndrome lymphoblastoid cell lines as detected by conventional cytogenetic analysis and fluorescence in situ hybridisation (FISH) technique |
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| Affiliation: | 1. Department of Biology, Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil;2. MGC, Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands;3. J.A. Cohen Institute of Radiopathology and Radiation Protection, Interuniversity Institute, Leiden, The Netherlands;1. Department of Immunology and Rheumatology, Immunogenomics and Inflammation Research Unit EA 4130, University of Lyon, Edouard Herriot Hospital, Lyon, France;2. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy;3. Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089;4. Department of Biological Sciences, University of North Carolina, Charlotte, North Carolina 28223;1. Carcinogenesis and Metastasis Research Branch, National Cancer Center, Gyeonggi, Republic of Korea;2. Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Gyeonggi, Republic of Korea;3. Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea;1. HealthStat Consulting, Inc., Seattle, WA, United States;2. University of Washington, Department of Epidemiology, Seattle, WA, United States;3. University of Illinois at Chicago, Center for Pharmacoepidemiology and Pharmacoeconomic Research, Chicago, IL, United States;4. PhenoPath Laboratories, Seattle, WA, United States;5. Swedish Cancer Institute, Department of Oncology, Seattle, WA, United States;1. Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA;2. Department of Biochemistry, University of Washington School of Medicine, Seattle, WA 98195, USA;3. Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA |
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| Abstract: | Several primary and transformed human cell lines derived from cancer prone patients are employed routinely for biochemical and DNA repair studies. Since transformation leads to some chromosomal instability a cytogenetic analysis of spontaneous chromosome aberrations in fibroblast cell lines derived from patients with Fanconi anaemia (FA), ataxia telangiectasia (AT), and in lymphoblastoid cell lines derived from patients with Bloom's syndrome (BS), was undertaken. Unstable aberrations were analysed in Giemsa stained preparations and the chromosome painting technique was used for evaluating the frequencies of stable aberrations (translocations). In addition, the frequency of sister-chromatid exchanges (SCEs) was determined in differentially stained metaphases. The SV40-transformed fibroblasts from these cell lines have higher frequencies of unstable aberrations than the primary fibroblasts. In the four lymphoblastoid cell lines derived from BS patients higher frequencies of spontaneously occurring chromosomal aberrations in comparison to normal TK6wt cells were also evident. The frequency of spontaneously occurring chromosome translocations was determined with fluorescence in situ hybridisation (FISH) and using DNA libraries specific for chromosomes 1, 2, 3, 4, 7, 8, 11, 14, 19, 20 and X. The translocation levels were found to be elevated for primary FA fibroblasts and lymphoblastoid cells derived from BS patients in comparison with control cell lines, hetero- and homozygote BS cell lines not differing in this respect. The SV40-transformed cell lines showed very high frequencies of translocations independent of their origin and almost every cell contained at least one translocation. In addition, clonal translocations were found in transformed control TK6wt and AT cell lines for chromosomes 20 and 14, respectively. The spontaneous frequencies of SCEs were similar in transformed fibroblasts derived from normal individuals and AT patients, whereas in SV40-transformed FA cells these were higher (4-fold). Among cell lines derived from BS patients, heterozygote lines behaved like control, whereas in homozygote cell lines very high frequencies of SCEs (about 12-fold) were evident. |
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