Studies on DNA repair defects in degenerative brain disease.
Using the alkaline filter elution technique we determined the induction and disappearance of single-strand breaks (SSB) in freshly isolated peripheral blood lymphocytes (PBL) from 43 Alzheimer disease (AD) patients and from 48 healthy, age- and sex-matched control subjects following in vitro exposure to N-ethyl-N-nitrosourea (ENU), methyl methanesulphonate (MMS), or gamma (gamma)-radiation. No differences in SSB disappearance between AD patients and controls were observed after treatment of PBL with MMS or gamma-rays. After treatment with ENU, however, the amount of SSB disappearance was significantly lower in PBL from familial, but not in PBL from sporadic AD patients. ENU repair in PBL from neurological controls was comparable to that found in normal age-matched controls, indicating that the lower amount of ENU repair in familial AD patients is not a consequence of neuronal degeneration. These tentative findings are discussed in relation to the aetiology of AD.
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Division on Aging, Harvard Medical School, Boston, MA 02215.
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D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D002478:Cells, Cultured; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D005038:Ethylnitrosourea; D005260:Female; D005720:Gamma Rays; D006801:Humans; D006816:Huntington Disease / Q000235:genetics; D008214:Lymphocytes / Q000187:drug effects / Q000528:radiation effects / Q000648:ultrastructure; D008297:Male; D008741:Methyl Methanesulfonate; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics
D008741:Methyl Methanesulfonate; D005038:Ethylnitrosourea