ABSTRACT
PURPOSE: In the mouse, paternal F0 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 (F3) CD1 mice with and without an acute 1.0 Gy paternal F0 radiation history each received an acute dose of 1.0 Gy from attenuated 137C n-rays. Kidney PKC and MAPK activities, and p53 protein levels were evaluated immediately following F3 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 F0 irradiation and increased PKC and MAPK activities following F3 irradiation irrespective of F0 radiation history. Kidney-derived fibroblasts had significant changes or strong trends for all selected endpoints based upon cross-interaction of F0 radiation history with F3 irradiation. Comet assays demonstrated significantly increased DNA damage in fibroblasts related to F0 irradiation and increased DNA damage following F3 irradiation. However, significantly decreased F3 irradiation damage was demonstrated based upon cross-interaction of F0 radiation. CONCLUSIONS: The data suggest that irradiation of paternal F0 Type B spermatogonia resulted in cellular reprogramming causing offspring with this radiation history to have altered responses to acute somatic n-irradiation.
Subject(s)
Kidney/radiation effects , Radiation Tolerance/genetics , Spermatogonia/radiation effects , Animals , Cell Division/genetics , Cell Division/radiation effects , Cells, Cultured , Crosses, Genetic , DNA Damage , Female , Fibroblasts/cytology , Fibroblasts/metabolism , Fibroblasts/radiation effects , Gamma Rays , Glutathione Transferase/metabolism , Kidney/cytology , Kidney/metabolism , Male , Mice , Mitogen-Activated Protein Kinases/metabolism , Protein Kinase C/metabolism , Spermatogenesis/genetics , Spermatogenesis/radiation effects , Tumor Suppressor Protein p53/metabolismABSTRACT
Gap junction intercellular communication (GJIC) is thought to play a role in the growth modulation that occurs within cell populations. An example of heterologous growth inhibition (competitive cell proliferation disadvantage) occurs within mouse aggregation chimeras comprised of irradiated and nonirradiated cleavage-stage embryos. The goal of this investigation was to test the hypothesis that GJIC participates in the competitive cell proliferation disadvantage that is expressed by the irradiated embryo in aggregation chimeras. Specifically, we tested the capacity of the GJIC inhibitor 18 alpha-glycyrrhetinic acid (AGA) to inhibit competitive cell proliferation disadvantage in heterologous aggregation chimeras that were comprised of one embryo that was irradiated with 1.0 Gy of (137)Cs gamma rays and then paired with one nonirradiated embryo. We found that AGA successfully inhibited fluorescent dye transfer between irradiated and nonirradiated embryos in heterologous chimeras. Chronic exposure to AGA prevented competitive cell proliferation disadvantage in these radiation chimeras, while exposure to AGA for the first 15 h of culture (prior to gap junction development) did not prevent competitive cell proliferation disadvantage. An unexpected observation was the apparent lack of any effect of inhibiting GJIC by exposure to AGA on blastocyst formation and cell number allocation in the two principal stem cell lineages of the preimplantation mammalian embryo, trophectoderm and inner cell mass.
