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 Al zheimer disease (AD). Cells were treated with either ultraviolet radia tion (UV) or the chemotherapeutic alkylating agent, nitrogen mustard ( HN2). DNA damage formation and repair were studied in the active dihyd rofolate reductase (DHFR) gene for the main lesions introduced by each of these two types of DNA damaging agents. The gene specific repair o f UV induced cyclobutane pyrimidine dimers in the human DHFR gene was 86% complete in the AD cells after 24 h of repair incubation. This rep air 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. Th e gene specific repair of HN2 induced lesions in the DHFR gene was com pleted 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. Th ese results indicate that familial AD fibroblasts have normal gene spe cific repair of both UV induced and HN2 induced DNA damage in active g enes.