Cellular reprogramming in the F3 mouse with paternal F0 radiation history.
OBJECTIVE
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.


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.
Vance
M M
MM
Institute of Toxicology and Environmental Health, University of California, Davis, CA 95616, USA.
Baulch
J E
JE
Raabe
O G
OG
Wiley
L M
LM
Overstreet
J W
JW
D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000528:radiation effects; D002478:Cells, Cultured; D003433:Crosses, Genetic; D004249:DNA Damage; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D005720:Gamma Rays; D005982:Glutathione Transferase / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics*; D013091:Spermatogenesis / Q000235:genetics / Q000528:radiation effects; D013093:Spermatogonia / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D005982:Glutathione Transferase; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases