Radiosensitivity and repair of the inactive X-chromosome. Insights from FISH and immunocytogenetics

J Surrallés, AT Natarajan

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10 Citations (Scopus)

Abstract

The inactive X-chromosome provides a unique opportunity to study the role of transcriptional activity and chromatin condensation in the repair of chromosome damage. We induced chromosome breakage in human lymphocytes with X-rays (1 or 2 Gy) in either G(0) and G(1) phase of the cell cycle, and in the presence or absence of an inhibitor of double strand break repair, adenine 9-beta-D-arabinofuranoside (Ara-A). Chromosomal aberrations involving the X-chromosome were detected by means of fluorescence in situ hybridization with an X-chromosome specific red painting probe. The activation status of the X-chromosomes involved in the chromosomal aberrations was determined by simultaneous immunocytogenetics with FITC-conjugated antibodies against BrdUrd incorporated at late S-phase to distinguish the late replicating inactive X-chromosome in green-yellow. This multicolor approach allowed us to study and compare breakage and the extent of repair in the active and inactive X-chromosome. Our data indicate that both chromosomes responded with a similar radiosensitivity. This observation was consistent at both X-ray doses and at the two stages of the cell cycle analyzed. However, the number of chromosomal aberrations involving the inactive X-chromosome was increased after repair inhibition with Ara-A. The differential sensitivity to repair inhibition was observed in G, after 1 Gy and in G, after 2 Gy, Thus, the activation status of the X-chromosome might be a source of heterogeneity in breakage and repair. These observations suggest that there is heterogeneous repair when the active and the inactive X-chromosomes are compared and that the observed fragility is the result of a compromise between the actual number of breaks induced in each chromosome and their differential processing. (C) 1998 Elsevier Science B.V. All rights reserved.
Original languageEnglish
Pages (from-to)117-124
Number of pages8
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume414
Issue number1-3
DOIs
Publication statusPublished - 1 May 1998

Keywords

  • AntiBrdU antibody
  • Ara-A
  • Fish
  • X-ray
  • Breakage
  • Chromatin
  • inactive X-chromosome
  • Repair

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