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Generation of Mice Derived from Induced Pluripotent Stem Cells
Published on: November 29, 2012
Cellular reprogramming in the F3 mouse with paternal F0 radiation history
M M Vance1, J E Baulch, O G Raabe
1Institute of Toxicology and Environmental Health, University of California, Davis, CA 95616, USA.
International Journal of Radiation Biology
|July 2, 2002
Summary
Paternal radiation exposure in mice caused cellular reprogramming, altering offspring responses to subsequent irradiation. This suggests inherited epigenetic changes impact DNA damage and cellular signaling pathways.
Area of Science:
- Radiation biology
- Epigenetics
- Somatic cell response
Background:
- Paternal irradiation of spermatogonia in mice induces biological effects in offspring.
- These effects are hypothesized to involve cellular reprogramming.
- Altered signaling kinase activities and protein levels are observed in offspring.
Purpose of the Study:
- To investigate if paternal irradiation reprograms cells.
- To determine if this reprogramming alters somatic cell responses to ionizing radiation.
- To examine the effects on kidney and fibroblast cells in F3 generation mice.
Main Methods:
- Third-generation (F3) mice with and without paternal F0 irradiation history received 1.0 Gy n-rays.
- Kidney PKC, MAPK activities, and p53 levels were measured post-irradiation.
- Fibroblast cultures were analyzed for signaling, protein levels, and DNA damage.
Main Results:
- Kidneys showed decreased PKC/MAPK activity and p53 levels due to F0 irradiation, with increased activity after F3 irradiation.
- Fibroblasts exhibited significant changes in endpoints due to the interaction of F0 history and F3 irradiation.
- DNA damage increased with F0 and F3 irradiation, but was significantly decreased by the combined F0 history and F3 irradiation.
Conclusions:
- Paternal F0 irradiation of spermatogonia induces cellular reprogramming.
- Offspring with this history show altered responses to acute somatic n-irradiation.
- Epigenetic modifications may mediate these transgenerational effects on radiation sensitivity.
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