Gene specific DNA repair of damage induced in familial Alzheimer disease cells by ultraviolet irradiation or by nitrogen mustard.
We have measured gene specific DNA repair in a normal human fibroblast cell line, and in fibroblast lines from two patients with familial Alzheimer disease (AD). Cells were treated with either ultraviolet radiation (UV) or the chemotherapeutic alkylating agent, nitrogen mustard (HN2). DNA damage formation and repair were studied in the active dihydrofolate reductase (DHFR) gene for the main lesions introduced by each of these two types of DNA damaging agents. The gene specific repair of UV induced cyclobutane pyrimidine dimers in the human DHFR gene was 86% complete in the AD cells after 24 h of repair incubation. This repair efficiency was similar to what we and others have found in normal human fibroblasts. After treatment of the AD cells with HN2, we found the frequency of HN2 induced lesions in the DHFR gene to be similar to the frequency in the transcriptionally inactive delta-globin gene. The gene specific repair of HN2 induced lesions in the DHFR gene was completed within 8-24 h in the normal fibroblast line and in the familial AD line, and the repair kinetics were similar for both cell lines. These results indicate that familial AD fibroblasts have normal gene specific repair of both UV induced and HN2 induced DNA damage in active genes.
Link
C J
CJ
Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, MD 20892.
Robbins
J H
JH
Bohr
V A
VA
D000544:Alzheimer Disease / Q000378:metabolism*; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D005347:Fibroblasts; D005914:Globins / Q000235:genetics; D006801:Humans; D008466:Mechlorethamine / Q000009:adverse effects*; D011740:Pyrimidine Dimers; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D011740:Pyrimidine Dimers; D008466:Mechlorethamine; D005914:Globins; D013762:Tetrahydrofolate Dehydrogenase