Influence of Prior Exposure to Low-Dose Adapting Radiation on Radiation-Induced Teratogenic Effects in Fetal Mice with VaryingTrp53Function

Abstract

Teratogenesis in tails and limb digits of fetal mice with varying Trp53 status was examined after exposure of pregnant females to 4 Gy gamma radiation with and without a prior 30-cGy exposure. Prior low-dose exposure modified the teratogenic effects of radiation in a manner dependent upon Trp53 status and gestation time. A 4-Gy exposure on gestation day 11 resulted in tail shortening and digit abnormalities. 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 gestation day 12 had no effect on the reduced tail length resulting from the 4-Gy exposure of Trp53(+/+) or Trp53(+/-) fetuses, but it 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 preirradiation could not be detected. However, the preirradiation did result in protection against in digit abnormalities in Trp53(+/-) fetuses. We conclude that radiation-induced teratogenesis reflects both Trp53-dependent and independent processes that lead to apoptosis, and these respond differently to prior adapting doses.

Teratogen-induced apoptotic cell death: Does the apoptotic machinery act as a protector of embryos exposed to teratogens?

“…At the same time, in many other studies, p53-positive embryos demonstrated a higher sensitivity to radiation-induced teratogenic insult than their p53 negative counterparts Mitchel et al, 2002), and the increased teratological sensitivity of these embryos was found to be associated with p53-mediated apoptosis (Kubota et al, 2000;Wang et al, 2000aWang et al, , 2000b.…”

Cardiovascular Changes in Atherosclerotic ApoE-Deficient Mice Exposed to Co60 (γ) Radiation

“…In this study, we exposed ApoE-deficient mice to radiation acutely and chronically to investigate toxicity mechanisms relevant to cardiovascular effects. For chronic exposures at 2 Gy, mice were exposed at 0.1 cGy/min, a dose rate selected on the basis of protective effects against chromosomal breaks in human cells [38], neoplastic transformation in mouse cells [39], and radiation-induced myeloid leukemia in mice [40].…”

An Examination of Radiation Hormesis Mechanisms Using a Multistage Carcinogenesis Model

“…Support for the possibility of hormetic effects from low doses of low-LET radiation comes from both in vivo animal carcinogenesis studies (Wang et al, 1998(Wang et al, , 2000Mitchel et al, 1999Mitchel et al, , 2002Mitchel et al, , 2003 as well as studies performed using cell cultures irradiated with low-LET radiation at very low doses rates. These in vitro experiments show a reduction of induced transformation frequencies at low doses to values below that observed spontaneously (Azzam et al, 1996;Redpath and Antoniono, 1998;Redpath et al, 2001Redpath et al, , 2003aRedpath et al, , 2003b.…”