Trp53 Activity Is Repressed in Radio-adapted Cultured Murine Limb Bud Cells

• Published in: JOURNAL OF RADIATION RESEARCH Vol. 52; no. 6; pp. 727 - 734
• Main Authors: Vares, Guillaume, Wang, Bing, Tanaka, Kaoru, Shang, Yi, Fujita, Kazuko, Hayata, Isamu, Nenoi, Mitsuru
• Format: Journal Article
• Language: English
• Published: England THE JAPAN RADIATION RESEARCH SOCIETY 2011; Oxford University Press
• Subjects: Adaptation, Physiological - radiation effects; Analysis; Animals; Apoptosis; Apoptosis - radiation effects; Extremities - embryology; Extremities - radiation effects; Female; Fetus - metabolism; Fetus - radiation effects; Ionizing radiation; Mice; Mice, Inbred ICR; Models, Biological; Pregnancy; Radiation Tolerance; Tumor Suppressor Protein p53 - antagonists & inhibitors; Tumor Suppressor Protein p53 - radiation effects
• DOI: 10.1269/jrr.10092
• EISSN: 1349-9157
• ISSN: 0449-3060

Understanding the effects of of ionizing radiation (IR) at low dose in fetal models is of great importance, because the fetus is considered to be at the most radiosensitive stage of the development and prenatal radiation might influence subsequent development. We previously demonstrated the existence of an adaptive response (AR) in murine fetuses after pre-exposure to low doses of X-rays. Trp53-dependent apoptosis was suggested to be responsible for the teratogenic effects of IR; decreased apoptosis was observed in adapted animals. In this study, in order to investigate the role of Trp53 in AR, we developed a new model of irradiated micromass culture of fetal limb bud cells, which replicated proliferation, differentiation and response to IR in murine embryos. Murine fetuses were exposed to whole-body priming irradiation of 0.3 Gy or 0.5 Gy at embryonic day 11 (E11). Limb bud cells (collected from digital ray areas exhibiting radiation-induced apoptosis) were cultured and exposed to a challenging dose of 4 Gy at E12 equivalent. The levels of Trp53 protein and its phosphorylated form at Ser18 were investigated. Our results suggested that the induction of AR in mouse embryos was correlated with a repression of Trp53 activity.