Threshold effect for teratogenic risk of radiation depends on dose-rate and p53-dependent apoptosis.
OBJECTIVE
To obtain evidence that the p53 gene is indispensable for reduction of high teratogenic risk of radiation at a high dose-rate to zero risk by lowering the dose-rate.


METHODS
Wild-type p53(+/+), heterozygous p53(+/-) and null p53(-/-) mice were exposed to gamma-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, 2 Gy y-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.


CONCLUSIONS
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.
Kato
F
F
Department of Radiation Biology & Health, School of Medicine, University of Occupational & Environmental Health, Kitakyushu, Japan. fumiok@med.uoeh-u.ac.jp
Ootsuyama
A
A
Nomoto
S
S
Kondo
S
S
Norimura
T
T
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002588:Cesium Radioisotopes / Q000009:adverse effects; D000013:Congenital Abnormalities / Q000209:etiology; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005333:Fetus / Q000528:radiation effects*; D005720:Gamma Rays / Q000009:adverse effects*; D005838:Genotype; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000528:radiation effects*; D012306:Risk; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D002588:Cesium Radioisotopes; D016159:Tumor Suppressor Protein p53