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)


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).


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