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Correction of Post-γ Ray DNA Repair Deficiency in Ataxia-Telangiectasia Complementation Group A Fibroblasts by Cocultivation with Normal Fibroblasts

  • M. C. Paterson
  • R. Mirzayans
Conference paper
Part of the NATO ASI Series book series (volume 77)

Abstract

Ataxia-telangiectasia (A-T) is a rare human recessively-inherited disorder characterized by, among other symptoms, a devastating and sometimes fatal reaction to conventional radiotherapy (Boder, 1985; Sedgwick and Boder, 1991). Radiation intolerance in vitro, as manifested by impaired colony-forming ability and exessive chromosomal instability, is universally displayed by cultured dermal fibroblasts and peripheral blood lymphocytes derived from A-T donors (Lehmann, 1982; Taylor, 1982; Paterson et al, 1984). As an extension of these radiobiological studies on A-T, we have recently conducted a detailed study on the deleterious effects of 4-nitroquinoline 1-oxide (4NQO), a partially radiomimetic carcinogen, on A-T fibroblast strains and have demonstrated that representative strains belonging to complementation groups A (AT2BE and AT3BI) and C (AT4BI) are defective in removal of a class of alkali-stable 4NQO-DNA adducts, whereas a group D strain (AT5BI) exhibits normal repair capacity (Mirzayans et al, 1989; Mirzayans and Paterson, 1991a). In this investigation, repair was monitored with the aid of 1-β-D-arabinofuranosylcytosine (araC), a potent inhibitor of DNA polymerases α and δ (Wist, 1979; Cleaver, 1984; Keeney and Linn, 1990). In this widely used approach, the extent of DNA strand breaks accumulating in cultures incubated with araC, following carcinogen treatment, becomes a measure of the efficiency to perform long-patch excision repair (Snyder et al., 1984; Cleaver, 1989; Mirzayans and Paterson, 1991b).

Keywords

Normal Fibroblast Normal Human Fibroblast GM38 Cell Fibroblast Strain Phospholipid Dependent Protein Kinase 
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

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • M. C. Paterson
    • 1
  • R. Mirzayans
    • 1
  1. 1.Molecular Oncology Program Department of MedicineCross Cancer InstituteEdmontonCanada

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