Radiation sensitivity of the gastrula-stage embryo: Chromosome aberrations and mutation induction in lacZ transgenic mice: The roles of DNA double-strand break repair systems

Autor: J. Buset, Arlette Michaux, Mieke Neefs, Paul P.W. van Buul, P. Jacquet, Annemarie van Duijn-Goedhart, Pieter Monsieurs, Peter Boer, Karine Reynaud, Sarah Baatout
Přispěvatelé: Belgian Nuclear Research Centre, Department of Toxicogenetics, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), École nationale vétérinaire - Alfort (ENVA), Radboud University [Nijmegen], European Commission FP5-GEMRATE FIGH-CT2002-00210, EU FP6-NOTE IP 036465, European Project: 249689,EC:FP7:Fission,FP7-Fission-2009,DOREMI(2010), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), École nationale vétérinaire d'Alfort (ENVA), Radboud university [Nijmegen], Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Mutation Research-Genetic Toxicology and Environmental Mutagenesis
Mutation Research-Genetic Toxicology and Environmental Mutagenesis, 2015, 792, pp.26-34. ⟨10.1016/j.mrgentox.2015.09.001⟩
Mutation Research-Genetic Toxicology and Environmental Mutagenesis, Elsevier, 2015, 792, pp.26-34. ⟨10.1016/j.mrgentox.2015.09.001⟩
ISSN: 1383-5718
Popis: International audience; At the gastrula phase of development, just after the onset of implantation, the embryo proper is characterized by extremely rapid cell proliferation. The importance of DNA repair is illustrated by embryonic lethality at this stage after ablation of the genes involved. Insight into mutation induction is called for by the fact that women often do not realize they are pregnant, shortly after implantation, a circumstance which may have important consequences when women are subjected to medical imaging using ionizing radiation. We screened gastrula embryos for DNA synthesis, nuclear morphology, growth, and chromosome aberrations (CA) shortly after irradiation with doses up to 2.5 Gy. In order to obtain an insight into the importance of DNA repair for CA induction, we included mutants for the non-homologous end joining (NHEJ) and homologous recombination repair (HRR) pathways, as well as Parp1-/- and p53+/− embryos. With the pUR288 shuttle vector assay, we determined the radiation sensitivity for point mutations and small deletions detected in young adults. We found increased numbers of abnormal nuclei 5 h after irradiation; an indication of disturbed development was also observed around this time. Chromosome aberrations 7 h after irradiation arose in all genotypes and were mainly of the chromatid type, in agreement with a cell cycle dominated by S-phase. Increased frequencies of CA were found for NHEJ and HR mutants. Gastrula embryos are unusual in that they are low in exchange induction, even after compromised HR. Gastrula embryos were radiation sensitive in the pUR288 shuttle vector assay, giving the highest mutation induction ever reported for this genetic toxicology model. On theoretical grounds, a delayed radiation response must be involved. The compromised developmental profile after doses up to 2.5 Gy likely is caused by both apoptosis and later cell death due to large deletions. Our data indicate a distinct radiation-sensitive profile of gastrula embryos, including some stage-specific aspects that are not as yet understood.
Databáze: OpenAIRE
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