In Vitro Correction of Cells from Patients with Mutagen Hypersensitivity

  • N. G. J. Jaspers
  • L. Roza
  • W. Vermeulen
  • A. Eker
  • R. D. F. M. Taalman
  • J. H. J. Hoeijmakers
  • D. Bootsma


An important strategy in the study of mutant cells, such as those from patients with an inherited hypersensitivity to UV or X-rays, is based on the principle of correction. In this contribution various approaches of in vitro correction are illustrated with complementation analysis of ataxia telangiectasia (AT) and with the introduction of wild-type protein extracts or yeast photoreactivating enzyme into xeroderma pigmentosum (XP) cells.

The combined results from genetic complementation studies in X-ray sensitive patients using the radioresistant DNA synthesis as a marker indicate the existence of six different complementation groups. Four of these (AB, C, D and E) are represented by AT patients and two (V1 and V2) harbour patients with the “Nijmegen Breakage syndrome”. A seventh separate category is formed by a number of AT patients with a normal inhibition of DNA synthesis by X-rays.

In XP cells a transient correction of the defect was accomplished by micro-injection of cell-free extracts from wild-type sources. Some properties of the factor correcting XP cells from complementation group A are described.

Micro-injection was also used to introduce the yeast photo-reactivating enzyme (PRE) into cells. After light-induced removal of pyrimidine dimers in injected cells the levels of UV-induced unscheduled DNA synthesis (UV-UDS) decreased only slowly. Kinetic studies suggest, that the average processing time of dimer excision is less than 1 hour in normal cells and more than 3 hours in some XP complementation groups.


Ataxia Telangiectasia Average Processing Time Nijmegen Breakage Syndrome NIJMEGEN Breakage Syndrome Patient Mutagen Hypersensitivity 
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Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • N. G. J. Jaspers
    • 1
  • L. Roza
    • 2
  • W. Vermeulen
    • 1
  • A. Eker
    • 1
  • R. D. F. M. Taalman
    • 3
  • J. H. J. Hoeijmakers
    • 1
  • D. Bootsma
    • 1
  1. 1.Laboratory of Cell Biology and GeneticsErasmus UniversityRotterdamThe Netherlands
  2. 2.Medical Biological LaboratoryRijswijkThe Netherlands
  3. 3.Department of Human GeneticsCatholic Univ.NijmegenThe Netherlands

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