Cytogenetic responses to G2 phase X-irradiation of cells from retinoblastoma patients

Fibroblast cell lines from 20 retinoblastoma (RB) patients with the hereditary bilateral form of disease compared with 16 lines from normal donors had a significantly higher chromatid aberration frequency (CAF), and more displaced and nondisplaced breaks per 100 metaphase cells after x-irradiation during the G2 phase of the cell cycle. The mean CAF was 39 ± 1.0, range 30–46, for cells from normal subjects, compared to a mean of 245.6, range 101–506, for cells from hereditary RB patients (p < 10−6). Of fibroblast lines from eight patients with unilateral RB, four had a CAF comparable to that of lines from normal donors (< 60) and four had a high CAF (> 130), resembling that of hereditary forms; two of the latter four lines were from patients with familial or deletion 13 forms of RB. Furthermore, in two families, PHA-stimulated blood lymphocytes from RB patients, one bilateral and one unilateral, and from certain unaffected first-degree relatives after G2 phase X-irradiation had a high CAF (⩾ 110) compared to a CAF (⩾ 53) of cells from three normal donors sampled at the same time. These results were shown not to be related to differences in cell cycle progression or initial extent of chromatid damage. The results suggest that the high frequency of chromatid aberrations in the cells from hereditary RB patients results from a genetic deficiency in DNA repair.