Cellular reprogramming in the F3 mouse with paternal F0 radiation history

Purpose: In the mouse, paternal F-0 acute irradiation of Type B spermatogonia produces biological effects in offspring, including altered signalling kinase activities and protein levels. It was hypothesized that these effects represented cellular reprogramming that would alter the response of somatic cells in these offspring to an acute ionizing radiation exposure. Materials and methods: Nineteen-day-old third generation (F-3) CD1 mice with and without an acute 1.0 Gy paternal F-0 radiation history each received an acute dose of 1.0 Gy from attenuated C-137 gamma-rays. Kidney PKC and MAPK activities, and p53 protein levels were evaluated immediately following F-3 irradiation. The same endpoints and DNA damage were evaluated in kidney-derived fibroblast primary cell cultures 3 weeks post-irradiation. Results : Kidneys had significantly decreased PKC and MAPK activities and p53 protein levels related to F-0 irradiation and increased PKC and MAPK activities following F-3 irradiation irrespective of F-0 radiation history. Kidney-derived fibroblasts had significant changes or strong trends for all selected endpoints based upon cross-interaction of F-0 radiation history with F-3 irradiation. Comet assays demonstrated significantly increased DNA damage in fibroblasts related to F-0 irradiation and increased DNA damage following F-3 irradiation. However, significantly decreased F-3 irradiation damage was demonstrated based upon cross-interaction of F-0 radiation. Conclusions : The data suggest that irradiation of paternal F-0 Type B spermatogonia resulted in cellular reprogramming causing offspring with this radiation history to have altered responses to acute somatic gamma-irradiation.