title: Prenatal radiation-induced limb defects mediated by Trp53-dependent apoptosis in mice.
abstract: We reported previously that in utero radiation-induced apoptosis in the predigital regions of embryonic limb buds was responsible for digital defects in mice. To investigate the possible involvement of the Trp53 gene, the present study was conducted using embryonic C57BL/6J mice with different Trp53 status. Susceptibility to radiation-induced apoptosis in the predigital regions and digital defects depended on both Trp53 status and the radiation dose; i.e., Trp53 wild-type (Trp53(+/+)) mice appeared to be the most sensitive, Trp53 heterozygous (Trp53(+/-)) mice were intermediate, and Trp53 knockout (Trp53(-/-)) mice were the most resistant. These results indicate that induction of apoptosis and digital defects by prenatal irradiation in the later period of organogenesis are mediated by the Trp53 gene. These findings suggest that the wild-type Trp53 gene may be an intrinsic genetic susceptibility factor that is responsible for certain congenital defects induced by prenatal irradiation.
authors.affiliation: Division of Radiobiology and Biodosimetry, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Ohyama
authors.forename: K
authors.initials: K
authors.lastname: Haginoya
authors.forename: T
authors.initials: T
authors.lastname: Odaka
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: I
authors.initials: I
authors.lastname: Hayata
mesh_terms: D000016:Abnormalities, Radiation-Induced / Q000235:genetics* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005313:Fetal Death / Q000473:pathology; D018878:Limb Buds / Q000473:pathology / Q000528:radiation effects; D017880:Limb Deformities, Congenital / Q000000981:diagnostic imaging / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011836:Radiation Tolerance / Q000235:genetics; D011859:Radiography; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53