X-ray-induced chromatid damage in cells from Down syndrome and Alzheimer disease patients in relation to DNA repair and cancer proneness

Topic: Brain proteins, microglia and lab models

Frequencies of chromatid aberrations in response to G2-phase x-irradiation were compared in PHA-stimulated blood lymphocytes from healthy control subjects, Down syndrome (DS) patients, and Alzheimer disease (AD) patients. In cells arrested with Colcemid immediately (0-30 min) after x-irradiation, DS, AD, and control cells showed similar high frequencies of chromatid breaks and gaps, representing unrepaired DNA strand breaks. Frequencies had decreased in AD and control cells arrested 30-90 min after irradiation. However, DS cells had two- to three-fold higher frequencies than AD or control cells. This result indicates deficient repair of the DNA damage in DS cells. Similar responses were obtained with lymphocytes from four of seven DS parents tested and with skin fibroblasts from DS patients compared to age-matched controls. Addition of 1-beta-D-arabinofuranosylcytosine (ara-C), an inhibitor of the repair polymerase, after x-irradiation during G2 phase increased the frequencies of chromatid breaks and gaps in lymphocytes from control and AD donors significantly more than in those from DS patients. This result indicates a deficiency in DS cells in incision at sites of x-ray-induced damage. Thus DS, like other cancer-prone genetic disorders, has a G2-phase DNA repair deficiency in strand break repair and also a second DNA repair deficiency in incision activity.

@article{sanford1993-8221609,
  author  = {Sanford, K. K. and Parshad, R. and Price, F. M. and Tarone, R. E. and Schapiro, M. B.},
  title   = {{X-ray-induced chromatid damage in cells from Down syndrome and Alzheimer disease patients in relation to DNA repair and cancer proneness}},
  journal = {Cancer genetics and cytogenetics},
  year    = {1993},
  doi     = {10.1016/0165-4608(93)90127-8},
  pmid    = {8221609},
  url     = {https://doi.org/10.1016/0165-4608(93)90127-8}
}

Key findings

• This result indicates deficient repair of the DNA damage in DS cells.
• Similar responses were obtained with lymphocytes from four of seven DS parents tested and with skin fibroblasts from DS patients compared to age-matched controls.
• Addition of 1-beta-D-arabinofuranosylcytosine (ara-C), an inhibitor of the repair polymerase, after x-irradiation during G2 phase increased the frequencies of chromatid breaks and gaps in lymphocytes from control and AD donors significantly more than in those from DS patients.
• This result indicates a deficiency in DS cells in incision at sites of x-ray-induced damage.

Why it matters

This laboratory study found that cells from Down syndrome patients had deficient repair of X-ray-induced DNA damage compared to Alzheimer's disease and control cells. It describes a cellular difference but does not test any treatment, cure, or prevention for Alzheimer's disease.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/0165-4608(93)90127-8
• PubMed: 8221609
• Original source →

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Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease Neurology · 1984-07-01 · usefulness score 58/100 · Getting a diagnosis
• Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome Annals of Neurology · 1985-03-01 · usefulness score 56/100 · Down syndrome and Alzheimer's

Later studies that cite this one

3 studies in the alzhub library list this one in their references.

• Evidence against increased oxidative DNA-damage in Down syndrome Neuroscience letters · 1997-10-01 · usefulness score 40/100 · Down syndrome and Alzheimer's
• Reduction of chromatin assembly factor 1 p60 and C21orf2 protein, encoded on chromosome 21, in Down syndrome brain Journal of neural transmission. Supplementum · 2003-01-01 · usefulness score 36/100 · Down syndrome and Alzheimer's
• Fluorescent light-induced chromatid breaks distinguish Alzheimer disease cells from normal cells in tissue culture Proceedings of the National Academy of Sciences of the United States of America · 1996-05-01 · usefulness score 36/100 · Down syndrome and Alzheimer's

Related studies in Down syndrome and Alzheimer's

• DNA damage and repair: relevance to mechanisms of neurodegeneration Journal of neuropathology and experimental neurology · 2008-05-01 · usefulness score 43/100
• Morphological and biochemical assessment of DNA damage and apoptosis in Down syndrome and Alzheimer disease, and effect of postmortem tissue archival on TUNEL Neurobiology of aging · 2000-07-01 · usefulness score 44/100
• Prolonged coenzyme Q10 treatment in Down syndrome patients: effect on DNA oxidation Neurobiology of aging · 2011-05-23 · usefulness score 39/100
• Hypersensitivity to ionizing radiation in cultured cells from Down syndrome patients Journal of the neurological sciences · 1985-05-01 · usefulness score 35/100
• Study of spindle microtubule reassembly in cells from Alzheimer and Down syndrome patients following exposure to colcemid Alzheimer disease and associated disorders · 1990-01-01 · usefulness score 30/100
• Mortality and cancer incidence among individuals with Down syndrome Archives of internal medicine · 2003-03-01 · usefulness score 52/100

Also tagged “down”

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• DYRK1A and Activity-Dependent Neuroprotective Protein Comparative Diagnosis Interest in Cerebrospinal Fluid and Plasma in the Context of Alzheimer-Related Cognitive Impairment in Down Syndrome Patients Biomedicines · 2022-06-10 · usefulness score 43/100 · Biomarkers
• Partial BACE1 reduction in a Down syndrome mouse model blocks Alzheimer-related endosomal anomalies and cholinergic neurodegeneration: role of APP-CTF Neurobiology of aging · 2015-12-02 · usefulness score 43/100 · Down syndrome and Alzheimer's
• B31-13 Circadian Rest-Activity Rhythm and Alzheimer’s Disease Biomarkers in Adults With Down Syndrome American Journal of Respiratory and Critical Care Medicine · 2026-05-01 · usefulness score 44/100 · Down syndrome and Alzheimer's

Similar studies

• Alzheimer-Related Cerebrovascular Disease in Down Syndrome 2020 · Brain scans and imaging
• Lack of detectable radiation hypersensitivity in lymphoblastoid cells from multiple pedigrees of familial Alzheimer disease 1993 · Down syndrome and Alzheimer's
• Detection of Alzheimer disease in individuals with Down syndrome 1995 · Down syndrome and Alzheimer's
• Alzheimer's Disease in Down Syndrome 2012 · Down syndrome and Alzheimer's
• Cerebrovascular pathology in Down syndrome and Alzheimer disease 2017 · Down syndrome and Alzheimer's
• Development of Alzheimer disease in Down syndrome individuals 1983 · Down syndrome and Alzheimer's

More on Down syndrome and Alzheimer's

• A review that covers this ground Disturbed homocysteine metabolism is associated with cancer Experimental & molecular medicine · 2019-02-21 · usefulness score 41/100
• Newest in this subject Differential endothelial cell remodeling in Down syndrome and APP duplication drives distinct blood brain barrier dysfunction bioRxiv · 2026-10-30 · Preprint — not yet peer-reviewed · usefulness score 16/100
• Newest in this subject Memory and Plasma pTau217 Refine Prognosis in Down Syndrome Annals of neurology · 2026-10-02 · Peer-reviewed · usefulness score 47/100

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