title: Influence of prior exposure to low-dose adapting radiation on radiation-induced teratogenic effects in fetal mice with varying Trp53 function.
abstract: Teratogenesis in tails and limb digits of fetal mice with varying Trp53 status was examined after exposure of pregnant females to 4 Gy gamma radiation with and without a prior 30-cGy exposure. Prior low-dose exposure modified the teratogenic effects of radiation in a manner dependent upon Trp53 status and gestation time. A 4-Gy exposure on gestation day 11 resulted in tail shortening and digit abnormalities. A 30-cGy exposure 24 h prior to a 4-Gy radiation exposure on day 11 reduced the extent of both digit abnormalities and the tail-shortening effects in Trp53(+/+) fetuses and also reduced tail shortening in Trp53(+/-) fetuses, but to a lesser extent. However, the pre-exposure enhanced the tail-shortening effects of 4 Gy in Trp53(-/-) fetuses. In contrast, a 30-cGy exposure given 24 h prior to a 4-Gy exposure on gestation day 12 had no effect on the reduced tail length resulting from the 4-Gy exposure of Trp53(+/+) or Trp53(+/-) fetuses, but it partly protected Trp53(-/-) fetuses against reduced tail length. A 4-Gy exposure alone on day 12 did not result in any increase in the frequency of digit abnormalities in Trp53(-/-) fetuses so any protective effect of the preirradiation could not be detected. However, the preirradiation did result in protection against in digit abnormalities in Trp53(+/-) fetuses. We conclude that radiation-induced teratogenesis reflects both Trp53-dependent and independent processes that lead to apoptosis, and these respond differently to prior adapting doses.
authors.affiliation: Radiation Biology and Health Physics Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Ontario, K0J 1J0 Canada. mitchelr@aecl.ca
authors.forename: R E J
authors.initials: RE
authors.lastname: Mitchel
authors.forename: J-A
authors.initials: JA
authors.lastname: Dolling
authors.forename: J
authors.initials: J
authors.lastname: Misonoh
authors.forename: D R
authors.initials: DR
authors.lastname: Boreham
mesh_terms: D000016:Abnormalities, Radiation-Induced / Q000209:etiology*; D000222:Adaptation, Physiological; D000818:Animals; D005260:Female; D005313:Fetal Death / Q000209:etiology; D017880:Limb Deformities, Congenital / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013623:Tail / Q000002:abnormalities*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53