Early stage embryos of mice are radiosensitive to death, but the survivors are born without malformations; however, fetuses at the midgestational stage are highly susceptible to malformation at high, but not low doses of radiation. In order to elucidate the mechanisms of tissue repair of radiation-induced teratogenic injury, we compared the incidence of radiation-induced malformations and abortions in wild type p53 (+/+) mice and p53 (−/−) mice with the deficient p53 gene. For the p53 (+/+) mice, an X-ray dose of 2 Gy given at a high dose-rate (450 mGy/min) to the fetuses at 9.5 days of gestation was highly lethal and considerably teratogenic, whereas for the p53 (−/−) mice the same treatment was only slightly lethal but highly teratogenic. However, when an equal dose of 2 Gy given at the same gestational period but at a 400-fold lower dose-rate (1.2 mGy/min), the dose was no longer teratogenic for the p53 (+/+) mice, which are capable of p53-dependent apoptosis, whereas it remained teratogenic for the p53 (−/−) mice, which are unable to carry out apoptosis. Hence, complete elimination of the teratogenic damage from the irradiated tissues requires the concerted cooperation of two mechanisms, p53-dependent apoptotic tissue repair as well as the well-known DNA repair.
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