Radiation-induced tissue abnormalities in fetal brain are related to apoptosis immediately after irradiation.
OBJECTIVE
To investigate the relation between the incidence of radiation-induced tissue abnormalities in fetal brain and the extent of p53-dependent apoptosis.


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 3.0 Gy, and the incidence was markedly increased following a dose of 2.25 and 3.75Gy 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.


CONCLUSIONS
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.
Kubota
Y
Y
Environmental and Toxicological Sciences Research Group, National Institute of Radiological Sciences, Chiba, Japan. y_kubota@nirs.go.jp
Takahashi
S
S
Sun
X Z
XZ
Sato
H
H
Aizawa
S
S
Yoshida
K
K
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D001921:Brain / Q000002:abnormalities / Q000196:embryology* / Q000473:pathology / Q000528:radiation effects*; D016923:Cell Death / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005313:Fetal Death / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D005838:Genotype; D020287:In Situ Nick-End Labeling; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D009474:Neurons / Q000528:radiation effects; D011247:Pregnancy; D013997:Time Factors