DNA Double-strand Breaks Measured by Pulsed-field Gel Electrophoresis in Irradiated Lymphocytes from Normal Humans and Those with Alzheimer's Disease

Abstract

We have previously found that radiation-induced chromosome aberrations (dicentrics) are more numerous in lymphocytes from Alzheimer's disease (AD) patients than in those from age-matched normal individuals (Tobi et al. 1990). To investigate this further, we have examined double-strand breaks (dsb) produced by γ-irradiation in the DNA of AD and normal lymphocytes by using pulsed-field gel electrophoresis. The percentage of DNA migrating into the gels is an indirect measure of the number of dsb; we have assayed the DNA content of sequential slices of the gel by direct fluorometry and have found that the percentage migrating is dose dependent. Our results show that the level of damage is similar in AD and normal lymphocytes and preliminary assays of the rate of repair suggest that the half-time is also similar, the value being > 1 h. The latter is consistent with the known rate of rejoining of chromosome fragments in interphase lymphocytes (Pantelias and Maillie 1985). The results suggest that at a gross level dsb repair is not impaired in AD cells; however, we cannot exclude the possibility that there is misrepair or non-repair of a small fraction of the dsb, which might account for the greater radiosensitivity of the AD cells.