Prenatal Radiation-Induced Teratogenesis and Adaptive Response Modified by p53 and General Caspase Inhibitors

抄録

Effects of p53 inhibitor pifithrin-alpha and general caspase inhibitor z-VAD-FMK on radiation-induced teratogenesis and adaptive response were studied in ICR mouse fetuses. Both inhibitors markedly postponed and suppressed early apoptosis in limb buds of E12 fetuses irradiated with 3.5 Gy of X-rays, while neither of them affected incidences of digital defects, prenatal and postnatal death. A priming dose of 0.3 Gy on E11 resulted in an adaptive response that dramatically reduced those detrimental effects of the challenging dose of 3.5 Gy on E12. Both inhibitors significantly suppressed the priming radiation-induced apoptosis, however, they did not suppressed the apoptosis induced by the challenging dose. The adaptive response was totally vanished with administration of either inhibitor. These findings indicate that temporary delay and suppression of apoptosis do not lead to the relief of late teratogenesis, while suppression of the priming radiation-induced apoptosis interrupt the induction of adaptive response. [J Radiat Res 44:448 (2003)]