We previously described an enhanced sensitivity for cell killing and γ-H2AX focus induction after both high-dose-rate and continuous low-dose-rate γ irradiation in 14 primary fibroblast strains derived from hereditary-type retinoblastoma family members (both affected RB1/- probands and unaffected RB1/ parents). Here we present G2-phase chromosomal radiosensitivity assay data for primary fibroblasts derived from these RB family members and five Coriell cell bank controls (four apparently normal individuals and one bilateral RB patient). The RB family members and two normal Coriell strains had significantly higher (∼1.5-fold, P < 0.05) chromatid-type aberration frequencies in the first postirradiation mitosis after doses of 50 cGy and 1 Gy of 137Cs γ radiation compared to the remaining Coriell strains. The induction of chromatid-type aberrations by high-dose-rate G2-phase γ irradiation is significantly correlated to the proliferative ability of these cells exposed to continuous low-dose-rate γ irradiation (reported in Wilson et al., Radiat. Res. 169, 483494, 2008). Our results suggest that these moderately radiosensitive individuals may harbor hypomorphic genetic variants in genomic maintenance and/or DNA repair genes or may carry epigenetic changes involving genes that more broadly modulate such systems, including G2-phase-specific DNA damage responses.
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging