Deficient DNA repair in amyotrophic lateral sclerosis cells

Abstract

We studied survival and DNA repair capacity in cultured sporadic ALS and control skin fibroblasts after treatment with DNA damaging agents producing different types of lesions. Mean survival in ALS and control fibroblasts was similar after exposure to ultraviolet (UV) light, x-rays and mitomycin C (MMC). Both mean survival and mean unscheduled (repair) DNA synthesis (UDS) were significantly reduced in ALS fibroblasts following treatment with the alkylating agent methyl methane sulfonate (MMS). These data suggest that ALS cells are relatively deficient in the repair of alkylation damage, possibly of apurinic/apyrimidinic sites, and that they are not unduly sensitive to DNA damage produced by UV light, x-rays and MMC. Normal survival and UDS seen in some patients' cells after MMS treatment indicate a spectrum of repair efficiency, and suggest heterogeneity of the biochemical defect in ALS.