Journal ArticleDOI
Susceptibility of Fanconi's anaemia fibroblasts to chromosome damage by carcinogens
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TLDR
Experiments in which viable FA fibroblasts were exposed to a direct-acting mutagen or carcinogen for a period of 6 d, ensuring chronic exposure of the cells during one or more cell cycles, until increased cell density inhibited further cell division.Abstract:
INDIVIDUALS with certain genetic syndromes associated with chromosome damage show markedly increased incidence of cancer1. In one such syndrome, Fanconi's anaemia (FA), chromosomal breakage and rearrangement has been found in lymphocytes and fibroblasts2,3 years before the development of malignant tumours. There is some evidence that cells from FA patients are especially sensitive to oncogenic agents. FA fibroblasts are abnormally susceptible to SV40 transformation4, and lymphocytes from patients show increased chromosome aberrations after exposure to ionising radiation5, or to alkylating agents6,7. In these reports, however, evaluation was based on cells which entered metaphase during brief and possibly toxic exposures to chemicals. We report here experiments in which FA fibroblasts were exposed to a direct-acting mutagen or carcinogen for a period of 6 d, ensuring chronic exposure of the cells during one or more cell cycles, until increased cell density inhibited further cell division. After subculture we could then assay chromosome damage in cells capable of entering a new cycle of cell division after removal from the chemical. We found that viable FA fibroblasts showed increases in chromosome aberrations after exposure to the mutagen or carcinogen at concentrations that had no effect in other cell strains tested. Since fibroblasts can be maintained in serial passage, their use in this protocol makes it possible to examine residual and possibly lasting effects of the treatment.read more
Citations
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Journal ArticleDOI
Hematopoietic reconstitution in a patient with fanconi's anemia by means of umbilical-cord blood from an hla-identical sibling
Eliane Gluckman,Hal E. Broxmeyer,Arleen D. Auerbach,Henry S. Friedman,Gordon W. Douglas,Agnès Devergie,Helene Esperou,Dominique Thierry,Gérard Socié,Pierre Lehn,Scott Cooper,Denis English,Joanne Kurtzberg,Judith Bard,Edward A. Boyse +14 more
TL;DR: It is necessary to select patients suitable for vaginal or laparoscopic mesh placement for Fanconi's anemia preoperatively on the basis of prior history and once they provide informed consent for surgery.
Journal ArticleDOI
Ionizing Radiation: Sources and Biological Effects
TL;DR: In this paper, the authors present an Ionizing Radiation Sources and Biological Effects (IRBE) study, in which the sources and biological effects of ionizing radiation are investigated and compared.
Journal ArticleDOI
Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells
Angel Raya,Ignasi Rodríguez-Pizà,Guillermo Guenechea,Rita Vassena,Susana Navarro,Maria J. Barrero,Antonella Consiglio,Maria Castella,Paula Río,Eduard Sleep,Federico Gonzalez,Gustavo Tiscornia,Elena Garreta,Trond Aasen,Anna Veiga,Inder M. Verma,Jordi Surrallés,Juan A. Bueren,Juan Carlos Izpisua Belmonte +18 more
TL;DR: It is shown that corrected Fanconi-anaemia-specific iPS cells can give rise to haematopoietic progenitors of the myeloid and erythroid lineages that are phenotypically normal, that is, disease-free.
Journal ArticleDOI
Involvement of Brca2 in DNA repair.
Ketan J. Patel,Veronica P.C.C. Yu,Hyunsook Lee,Anne E. Corcoran,Fiona C Thistlethwaite,Martin J. Evans,William H. Colledge,Lori Friedman,Bruce A.J. Ponder,Ashok R. Venkitaraman +9 more
TL;DR: Findings define a function of Brca2 in DNA repair, whose loss precipitates replicative failure, mutagen sensitivity, and genetic instability reminiscent of Bloom syndrome and Fanconi anemia.
Journal ArticleDOI
How the Fanconi Anemia Pathway Guards the Genome
TL;DR: The current understanding of how the Fanconi Anemia pathway components participate in DNA repair is reviewed and the mechanisms that regulate this pathway to ensure timely, efficient, and correct restoration of chromosomal integrity are discussed.
References
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Journal Article
A high susceptibility of Fanconi's anemia to chromosome breakage by DNA cross-linking agents.
Masao S. Sasaki,Akira Tonomura +1 more
TL;DR: Peripheral blood lymphocytes of patients with Fanconi9s anemia were tested for their susceptibility to chromosome breakage by caffeine, chloramphenicol, actinomycin D, methylmethanesulfonate, nitrogen mustard and mitomycin C, and the specifically increased susceptibility to these compounds is interpreted as an indication that the FA cells are defective in the repair mechanism to tolerate the cross-links produced in their DNA.
Journal ArticleDOI
Susceptibility of human diploid fibroblast strains to transformation by SV40 virus.
TL;DR: A quantitative system has been developed for the study of transformation of human diploid fibroblasts in culture by two oncogenic viruses, SV40 and the E46 strain of adeno 7-SV40 "hybrid" virus.
Journal ArticleDOI
Induction by alkylating agents of sister chromatid exchanges and chromatid breaks in Fanconi's anemia.
TL;DR: The results suggest that chromosomal breaks and rearrangements in Fanconi's anemia lymphocytes may result from a defect in a form of repair of DNA damage.
Journal ArticleDOI
Somatic rearrangement of chromosome 14 in human lymphocytes.
TL;DR: It is hypothesize that structural rearrangement of 14q is directly related to abnormal growth of lymphocytes and that it may be a step toward the development of lymphoid malignancies.
Journal ArticleDOI
Chromosome Abnormalities in Constitutional Aplastic Anemia
TL;DR: In 1927 the condition now known as Fanconi's aplastic anemia was first described in 3 brothers with pancytopenia and multiple congenital anomalies.
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A high susceptibility of Fanconi's anemia to chromosome breakage by DNA cross-linking agents.
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