Wilson, P. F., Nagasawa, H., Warner, C. L., Fitzek, M. M., Little, J. B. and Bedford, J. S. Radiation Sensitivity of Primary Fibroblasts from Hereditary Retinoblastoma Family Members and Some Apparently Normal Controls: Colony Formation Ability during Continuous Low-Dose-Rate Gamma Irradiation. Radiat. Res. 169, 483–494 (2008).
We previously described an enhanced sensitivity for cell killing and G1-phase cell cycle arrest after acute γ irradiation in primary fibroblast strains derived from 14 hereditary-type retinoblastoma family members (both affected RB1 /− probands and unaffected RB1 / parents) as well as distinctive gene expression profiles in unirradiated cultures by microarray analyses. In the present study, we measured the colony formation ability of these cells after exposure to continuous low-dose-rate (0.5–8.4 cGy/h) 137Cs γ radiation for a 2-week growth period. Fibroblasts from all RB family members (irrespective of RB1 genotype) and from 5 of 18 apparently normal Coriell cell bank controls were significantly more radiosensitive than the remaining apparently normal controls. The average dose rates required to reduce relative survival to 10% and 1% were ∼3.1 and 4.7 cGy/h for the Coriell control strains with normal radiosensitivity and ∼1.4 and 2.5 cGy/h for the radiosensitive RB family member and remaining apparently normal Coriell control strains. The finding that a significant proportion of fibroblast strains derived from apparently normal individuals are sensitive to chronic low-dose-rate irradiation indicates such individuals may harbor hypomorphic genetic variants in genomic maintenance and/or DNA repair genes that may likewise predispose them or their children to cancer.