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Radiosensitive target in the mouse embryo chimera assay: implications that the target involves autocrine growth
J M Peters1, E C Tsark, L M Wiley
1Institute of Toxicology and Environmental Health, School of Medicine, University of California, Davis 95616-8615, USA.
Radiation Research
|June 1, 1996
Summary
Irradiated mouse embryos show a reduced proliferation rate, but this disadvantage is reversed by insulin-like growth factor II (IGF-II) or insulin. Epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) did not offer the same protection, suggesting differential receptor sensitivity to radiation.
Area of Science:
- Developmental Biology
- Radiation Biology
- Cell Signaling
Background:
- Mouse preimplantation embryos express epidermal growth factor receptor (EGF receptor) and insulin-like growth factor I receptor (IGF-I receptor).
- Embryo-expressed ligands IGF-II and TGF-alpha activate these receptors, influencing cell proliferation and differentiation.
- Ionizing radiation can impair embryo development, potentially through effects on these growth factor receptors.
Purpose of the Study:
- To investigate if impaired IGF-I receptor and/or EGF receptor function contribute to radiation-induced competitive cell proliferation disadvantage in mouse embryos.
- To determine if specific growth factors can rescue irradiated embryos from this disadvantage.
Main Methods:
- Cleavage-stage mouse embryos were irradiated (0.5 or 1.0 Gy) and aggregated with non-irradiated embryos to form chimeras.
- Chimeras were cultured in media with or without IGF-II, insulin, EGF, or TGF-alpha.
- Cell proliferation disadvantage in irradiated embryos within chimeras was assessed.
Main Results:
- IGF-II or insulin completely eliminated the cell proliferation disadvantage in irradiated embryos within chimeras.
- EGF or TGF-alpha failed to rescue irradiated embryos from the competitive proliferation disadvantage.
- In non-chimera cultures, IGF-II and TGF-alpha increased blastocoele formation but not cell number in irradiated embryos.
Conclusions:
- Ligands for the IGF-I receptor (IGF-II, insulin) can rescue irradiated embryos from competitive cell proliferation disadvantage, unlike EGF receptor ligands.
- Ionizing radiation affects IGF-I receptor and EGF receptor functions differently regarding competitive cell proliferation.
- EGF receptor-dependent stimulation of proliferation and differentiation are differentially affected by radiation in preimplantation embryos.