Radiation-induced tissue abnormalities in fetal brain are related to apoptosis immediately after irradiation

Purpose : To investigate the relation between the incidence of radiation-induced tissue abnormalities in fetal brain and the extent of p53-dependent apoptosis. Materials and Methods : Pregnant mice with wild-type p53(+/+), heterozygous p53(+/-) and homozygous mutant p53(-/-) fetuses received whole-b...

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Bibliographic Details
Published in:International journal of radiation biology 2000, Vol.76 (5), p.649-659
Main Author: Kubota, S. Takahashi, X.-Z. Sun, H. Sato, S. Aizawa, K. Yoshida, Y.
Format: Article
Language:English
Subjects:
Animals
Apoptosis - genetics
Apoptosis - radiation effects
Brain - abnormalities
Brain - embryology
Brain - pathology
Brain - radiation effects
Cell Death - radiation effects
Cell Survival - radiation effects
Dose-Response Relationship, Radiation
Female
Fetal Death - genetics
Genes, p53 - genetics
Genotype
In Situ Nick-End Labeling
Mice
Mice, Inbred C3H
Mice, Knockout
Neurons - radiation effects
Pregnancy
Time Factors
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Summary:Purpose : To investigate the relation between the incidence of radiation-induced tissue abnormalities in fetal brain and the extent of p53-dependent apoptosis. Materials and Methods : Pregnant mice with wild-type p53(+/+), heterozygous p53(+/-) and homozygous mutant p53(-/-) fetuses received whole-body X-irradiation on day 13 of gestation. The extent of apoptosis 6 hr after irradiation and the incidence of tissue abnormalities 3 days after irradiation in the brain were evaluated by histological examination of brain mantle. Results : The percentage of apoptotic cells increased linearly with dose in p53(+/+) and p53(+/-) fetuses, but no increase was found in p53(-/-). Approximately twice the dose was necessary in p53(+/-) fetuses to induce an apoptotic response to the extent observed in p53(+/+). Fetuses with brain-tissue abnormalities, such as a destroyed ventricular lining and rosettes with a central hollow appeared at a dose of 1.5 and 3.0Gy, and the incidence was markedly increased following a dose of 2.25 and 3.75 Gy in p53(+/+) and p53(+/-) mice, respectively, but no fetus with tissue abnormalities appeared in p53(-/-) at up to 3.75 Gy. Approximately twice the dose was necessary in p53(+/-) fetuses to induce brain-tissue abnormalities to the extent seen in p53(+/+) mice. Conclusion : The extent of apoptosis 6 hr after irradiation and the incidence and severity of brain-tissue abnormalities 3 days after irradiation corresponded well, suggesting that radiation-induced tissue abnormalities, such as destroyed ventricular lining, deranged glial fibre and appearance of rosettes in fetal brain were closely related to apoptosis seen 6 hr after irradiation.
ISSN:0955-3002
1362-3095
DOI:10.1080/095530000138312