Threshold effect for teratogenic risk of radiation depends on dose-rate and p53-dependent apoptosis

F. Kato, A. Ootsuyama, S. Nomoto, S. Kondo, T. Norimura

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Abstract

Purpose: To obtain evidence that the p53 gene is indispensable for reduction of high teratogenic risk of radiation at a high doserate to zero risk by lowering the dose-rate. Materials and methods: Wild-type p53(+/+), heterozygous p53(+/-) and null p53(-/-) mice were exposed to γ-rays at high or low dose-rates during days 9.5-10.5 of gestation. The incidence of malformations and prenatal deaths was studied. Frequencies of cells dying by apoptosis were measured during or after protracted irradiation. Results: After irradiation with 2 Gy, the frequency of apoptotic cells increased to 20% for p53(+/+) mice and did not increase at all for p53(-/-) mice. For p53(+/+) mice, 2Gy γ-rays induced 70% malformations when given at 1.06 Gy/min, but no malformations above the control when given at 1.2 mGy/min. In contrast, after irradiation of p53(-/-) foetuses with 2 Gy at 1.2mGy/min, the incidence of malformations increased 12% above control levels. Conclusion: Foetal irradiation with 2 Gy at 1.2 mGy/min was not teratogenic for p53(+/+) mice but teratogenic for p53(-/-) mice. This indicates that the p53 gene is indispensable for a threshold effect in the risk of radiation at low doses or dose-rates.

Original languageEnglish
Pages (from-to)13-19
Number of pages7
JournalInternational Journal of Radiation Biology
Volume77
Issue number1
DOIs
Publication statusPublished - Feb 5 2001

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All Science Journal Classification (ASJC) codes

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

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