An in vitro investigation of genetic susceptibility to cancer in diploid fibroblasts from retinoblastoma patients

Thirty‐two diploid fibroblast strains from individuals with the three forms of retinoblastoma were examined with an in vitro clonogenic survival assay to determine their sensitivity to killing by X rays. Strains from sporadic unilateral retinoblastoma patients and normal controls were indistinguishable from one another (group D₀'s = 147 ± 15 rads and 146 ± 5 rads, respectively) while the strains from patients with the hereditary form of the disease were significantly more X‐ray sensitive (D₀ = 111 ± 12). Strains derived from individuals with the D‐deletion form of the disease resembled the hereditary strains with respect to sensitivity and heterogeneity, suggesting a possible, common etiology for these two forms of the disease. A DNA‐repair defect is hypothesized as reflected by the observed hypersensitivity to X‐irradiation in these cells. We suggest that this defect may be associated with the enhanced frequency of spontaneous and radiationinduced second tumors seen in some retinoblastoma patients.