A cytogenetic assay for DNA repair capacity of cells during phases of the cell cycle, particularly G1 and G2, has been developed. The G2 repair assay was applied to skin fibroblasts or Phytohemagglutinin (PHA)- stimulated peripheral blood lymphocytes from patients with genetic predisposition to cancer. Fibroblast cell lines from retinoblastoma (RB) patients with the hereditary form of disease compared with normal controls showed a significantly higher frequency of chromatid breaks and gaps representing unrepaired DNA strand breaks when examined 0.5 to 1.5 h after x-irradiation. Limited studies of PHA-stimulated blood lymphocytes also showed abnormally high frequencies in unaffected carriers of the defective RB gene. as well as in one bilateral case and one of the parents. It was shown that the difference in aberration frequencies between RB and normal cells cannot be explained by differential perturbation of the cell cycle or differences in G2 phase delay. The results are consistent with a defect in processing DNA damage in cells from hereditary RB patients. In addition. DNA repair capacities were examined both during G1 and G2 in skin fibroblasts from patients with neurodegenerative diseases including Cockayne's syndrome. Down's syndrome and Alzheimer's disease (AD). the latter both familial and sporadic in origin. Defective removal of DNA damage from cells of patients with. or destined to develop. Alzheimer's disease (AD) was revealed through use of DNA-repair inhibitors. The defect may be pathogenic and provides a basis for presymptomatic testing and a rationale for devising therapeutic trials.
