Alzheimer disease fibroblasts are hypersensitive to the lethal effects of a DNA-damaging chemical.
A group of fibroblast lines from three patients with the sporadic form of Alzheimer disease (AD) showed a small but statistically significant hypersensitivity to the lethal effects of the DNA-damaging chemical N-methyl-N'-nitro-nitrosoguanidine (MNNG) when compared with lines from eight normal control subjects. A fibroblast line from a patient with a dominantly inherited form of familial AD had a hypersensitivity similar to that of the three sporadic AD lines. However, fibroblast lines from a group of five patients with spinal muscular atrophy (SMA) were not hypersensitive to the chemical, demonstrating that not every primary neuronal degeneration manifests hypersensitivity to this chemical. These findings are consistent with the possibility that a defect in DNA-repair mechanisms may be the cause of the in vitro hypersensitivity, as well as the premature death of neurons in vivo, in both the sporadic and familial forms of AD.
D000544:Alzheimer Disease / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004260:DNA Repair; D005260:Female; D006801:Humans; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D009133:Muscular Atrophy / Q000235:genetics; D009154:Mutation / Q000187:drug effects
D008769:Methylnitronitrosoguanidine