TY - JOUR
T1 - Threshold effect for teratogenic risk of radiation depends on dose-rate and p53-dependent apoptosis
AU - Kato, F.
AU - Ootsuyama, A.
AU - Nomoto, S.
AU - Kondo, S.
AU - Norimura, T.
N1 - Funding Information:
The authors thank Drs K. Fujikawa, T. Nomura, S. Matsuda, J. Muckerheide, M. Pollycove and T. Rockwell for comments and suggestions during preparation ofthe manuscript, Drs M. Katsuki and Y. Gondo for supplying transgenic mice, A. Zaitsu for making specimens, and H. Kakihara, M. Morita and R. Taketani for excellent technical assistance. The work was supported in part by Grants-in-Aid to T.N. for ScientiŽ c Research from the Ministry of Education, Science, Sports and Culture, Japan (09480128).
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1080/09553000010001899
DO - 10.1080/09553000010001899
M3 - Article
C2 - 11213346
AN - SCOPUS:0035139637
SN - 0955-3002
VL - 77
SP - 13
EP - 19
JO - International Journal of Radiation Biology
JF - International Journal of Radiation Biology
IS - 1
ER -