DNA DOUBLE-STRAND BREAKS MEASURED BY PULSED-FIELD GEL-ELECTROPHORESISIN IRRADIATED LYMPHOCYTES FROM NORMAL HUMANS AND THOSE WITH ALZHEIMERS-DISEASE

We have previously found that radiation-induced chromosome aberrations (dicentrics) are more numerous in lymphocytes from Alzheimer's diseas e (AD) patients than in those from age-matched normal individuals (Tob i et al. 1990). To investigate this further, we have examined double-s trand breaks (dsb) produced by gamma-irradiation in the DNA of AD and normal lymphocytes by using pulsed-field gel electrophoresis. The perc entage of DNA migrating into the gels is an indirect measure of the nu mber of dsb; we have assayed the DNA content of sequential slices of t he gel by direct fluorometry and have found that the percentage migrat ing is dose dependent. Our results show that the level of damage is si milar 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 ch romosome fragments in interphase lymphocytes (Pantelias and Maillie 19 85). The results suggest that at a gross level dsb repair is not impai red in AD cells; however, we cannot exclude the possibility that there is misrepair or non-repair of a small fraction of the dsb, which migh t account for the greater radiosensitivity of the AD cells.