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Somatic Cell and Molecular Genetics

, Volume 22, Issue 5, pp 393–402 | Cite as

Roberts syndrome fibroblasts showing cisplatin hypersensitivity have normal host cell reactivation of cisplatin-treated adenovirus and normal capacity of cisplatin-treated cells for adenovirus DNA synthesis

  • Kelly Davis
  • Darrell J. Tomkins
  • Andrew J. Rainbow
Article

Abstract

Roberts syndrome (RS) is a rare, recessively inherited disorder characterized by growth retardation, limb reductions and craniofacial deformities. Cells from a subset of afflicted individuals, termed RS+, display unusual separation or puffing of the heterochromatic regions of their chromosomes and are hypersensitive to several DNA-damaging agents including mitomycin C (MMC) and cisplatin, both of which can induce interstrand crosslinks in DNA. For this reason, we have investigated the ability of RS+ fibroblasts to repair cisplatin-induced DNA lesions using adenovirus as a probe. Host cell reactivation of cisplatin-treated adenovirus (Ad) was significantly reduced in nucleotide excision repair (NER)-deficient xeroderma pigmentosum (XP) cells but was normal in the two RS+ fibroblast strains and the Fanconi's anemia (FA) fibroblast strain tested. The capacity of cisplatin-treated cells for Ad DNA synthesis was reduced in XP and FA cells compared to normal human cells, but was not reduced in RS+ cells. These results indicate that the hypersensitivity of RS+ cells to cisplatin is not due to a deficiency in NER nor due to a deficiency in the pathway which leads to cisplatin hypersensitivity in FA cells. It is possible that the abnormal heterochromatin organisation of RS+ cells selectively renders the heterochromatic regions of the genome more susceptible to mutagen damage and/or less available for repair.

Keywords

Nucleotide Excision Repair Heterochromatic Region Xeroderma Pigmentosum Normal Human Cell Fibroblast Strain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Kelly Davis
    • 1
  • Darrell J. Tomkins
    • 1
    • 2
  • Andrew J. Rainbow
    • 1
    • 3
  1. 1.Departments of BiologyMcMaster UniversityHamiltonCanada
  2. 2.Departments of Pathology, PediatricsMcMaster UniversityHamiltonCanada
  3. 3.Departments of RadiologyMcMaster UniversityHamiltonCanada

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