Essential role of p53 gene in apoptotic tissue repair for radiation-induced teratogenic injury

Toshiyuki Norimura, Fumio Kato, Satoshi Nomoto

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)423-429
Number of pages7
JournalInternational Congress Series
Volume1236
Issue numberC
DOIs
Publication statusPublished - Jul 1 2002
Externally publishedYes

Fingerprint

p53 Genes
Radiation
Wounds and Injuries
Fetus
Apoptosis
Induced Abortion
DNA Repair
Embryonic Structures
X-Rays
Pregnancy
Incidence

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Essential role of p53 gene in apoptotic tissue repair for radiation-induced teratogenic injury. / Norimura, Toshiyuki; Kato, Fumio; Nomoto, Satoshi.

In: International Congress Series, Vol. 1236, No. C, 01.07.2002, p. 423-429.

Research output: Contribution to journalArticle

Norimura, Toshiyuki ; Kato, Fumio ; Nomoto, Satoshi. / Essential role of p53 gene in apoptotic tissue repair for radiation-induced teratogenic injury. In: International Congress Series. 2002 ; Vol. 1236, No. C. pp. 423-429.
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