PARENT SESSION
1:30 PM to 3:30 PM
Wednesday, April 24, 2002
Poster Session 26 Apoptosis
Room: Nevada Exhibition Center

(P31-308) Radiation Induced Teratogenic Effects in Fetal Mice with Varying Trp53 Function: Influence of Prior Radiation or Heat Stress.

Mitchel, R.^*,1, Dolling, J-A.¹, Misonoh, J.², Boreham, D.³, ¹ Atomic Energy of Canada Limited, Chalk River, ON Canada² Central Research Institute of Electric Power Industry, Abiko City, Japan³ Medical Physics and Applied Radiation Sciences, Hamilton, ON Canada

ABSTRACT-
Teratogenesis in tails and limb digits of fetal mice with varying Trp53 status was examined after a 4 Gy ⁶⁰Co- radiation exposure, with and without a prior 30 cGy exposure or a mild 40.5°C, 60 min heat stress. A 4 Gy irradiation earlier in gestation (day 11) produced greater effects than later (day 12) exposure, but in both cases the maximum teratogenic effect of radiation occurred in Trp53 +/+ fetuses, the minimum in Trp53 -/- fetuses and intermediate effects in Trp53 +/- fetuses, indicating dominance of Trp53 dependent apoptosis. Heat stress 24 h prior to radiation on day 11 did not alter the teratogenic effects of radiation in Trp53 +/+ or +/- fetuses, but reduced the effects in the Trp53 -/- fetuses. These results indicate no effect of mild heat on Trp53 dependent apoptotic responses to radiation, but heat-induced protection of Trp53 independent apoptotic processes. Conversely, on gestational day 12, heat stress 24 h prior to radiation exposure had a large amplifying effect in Trp53 +/+ or +/- fetuses but a diminished effect in Trp53-/- fetuses. A 30 cGy exposure 24 h prior to a 4 Gy radiation exposure on day 11 reduced the extent of both digit abnormalities and the tail shortening effects in Trp53 +/+ fetuses, and also reduced tail shortening in Trp53 +/- fetuses, but to a lesser extent. However, the pre-exposure enhanced the tail shortening effects of 4 Gy in Trp53 -/- fetuses. In contrast, a 30 cGy exposure given 24 h prior to a 4 Gy exposure on gestational day 12 had no effect on the reduced tail length resulting from the 4 Gy exposure of Trp53 +/+ or Trp53 +/- fetuses, but partly protected Trp53 -/- fetuses against reduced tail length. A 4 Gy exposure alone on day 12 did not result in any increase in the frequency of digit abnormalities in Trp53 -/- fetuses so any protective effect of the pre-irradiation could not be detected. However, the pre-irradiation did result in protection against digit abnormalities in Trp53 +/- fetuses. Radiation-induced teratogenesis apparently reflects both Trp53 dependent and independent apoptotic processes, and these respond differently to prior heat stress or prior adapting doses in a manner dependent upon gestational time.

KEYWORDS: Trp53, Teratogenesis, Mice, adaption