TY - JOUR
T1 - Deficient DNA repair in amyotrophic lateral sclerosis cells
AU - Tandan, R.
AU - Robison, S. H.
AU - Munzer, J. Scott
AU - Bradley, Walter G.
N1 - Funding Information:
Supported by research grants from the ALS Society of America (RT and WGB), the National ALS Foundation (RT) and the Sandoz Foundation of America (SHR) Address for correspondence and reprint requests: Dr. Tandan, Department of Neurology, C-454 Given Building, University of Vermont College of Medicine, Burlington, VT 05401, U.S.A.
PY - 1987/6
Y1 - 1987/6
N2 - 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.
AB - 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.
KW - Alkylating agent
KW - Amyotrophic lateral sclerosis
KW - Cell survival
KW - Deoxyribonucleic acid repair
KW - Fibroblasts
KW - Methyl methane sulfonate
KW - Unscheduled deoxyribonucleic acid synthesis
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U2 - 10.1016/0022-510X(87)90272-3
DO - 10.1016/0022-510X(87)90272-3
M3 - Article
C2 - 3112312
AN - SCOPUS:0023186054
VL - 79
SP - 189
EP - 203
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
IS - 1-2
ER -