Radioresistant DNA synthesis and human genetic diseases

Topic: Brain proteins, microglia and lab models

Sixty-eight human fibroblast cell strains were assayed for radioresistant DNA synthesis (RDS), which is defined here as the absence of a steep component of inhibition of DNA synthesis in a dose-response curve when rate of DNA synthesis is plotted against radiation doses from 0 to 20 Gy or more. Twenty-seven strains from patients who were previously diagnosed to have ataxia-telangiectasia (AT) were positive for this feature. Among the cell strains that did not show RDS were two from AT obligate heterozygotes (i.e., the parents of AT patients), two from patients with Alzheimer disease, two from patients with Friedreich ataxia, one from a patient with Bloom syndrome, one from a patient with Down syndrome, and six from patients with various immunodeficiencies. Four strains demonstrated RDS that was less pronounced than in most AT cells: one was from a patient with Nijmegen breakage syndrome, one was from a patient without ataxia but with choreiform movement disorder, telangiectasia, and elevated concentrations of alpha-fetoprotein in the blood, and two were from AT patients. RDS therefore is not a necessary trait of human genetic diseases that involve radiosensitivity or immunodeficiency. Although recent reports suggest that some AT patients do not exhibit RDS, we found RDS in all the AT cells we tested.

@article{young1989-2722185,
  author  = {Young, B. R. and Painter, R. B.},
  title   = {{Radioresistant DNA synthesis and human genetic diseases}},
  journal = {Human genetics},
  year    = {1989},
  doi     = {10.1007/bf00284040},
  pmid    = {2722185},
  url     = {https://doi.org/10.1007/bf00284040}
}

Key findings

• Four strains demonstrated RDS that was less pronounced than in most AT cells: one was from a patient with Nijmegen breakage syndrome, one was from a patient without ataxia but with choreiform movement disorder, telangiectasia, and elevated concentrations of alpha-fetoprotein in the blood, and two were from AT patients.
• Although recent reports suggest that some AT patients do not exhibit RDS, we found RDS in all the AT cells we tested.

Why it matters

This laboratory study tested fibroblast cells for radioresistant DNA synthesis and found it in ataxia-telangiectasia cells but not in the two Alzheimer disease cells or the one Down syndrome cell tested. It is a small cell study unrelated to treating or preventing Alzheimer's disease.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1007/bf00284040
• PubMed: 2722185
• Original source →

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