PARENT SESSION
1:30 PM to 3:30 PM
Tuesday, April 23, 2002
Poster Session 18 Oncogenic Transformation in vitro & in vivo
Room: Nevada Exhibition Center

(P23-255) Low Doses of Radiation Increase the Latency of Spontaneous Cancers in Cancer Prone Trp53 Heterozygous Mice.

Mitchel, R.^*,1, Jackson, J.¹, Carlisle, S.¹, ¹ Atomic Energy of Canada Limited, Chalk River, ON Canada

ABSTRACT-
Mice that are heterozygous for defects in Trp53 are known to be cancer prone, spontaneously developing a variety of cancer types leading to premature death. The effect of low doses of ⁶⁰Co- radiation (10 or 100 mGy) delivered at a low dose rate (0.5 mGy/min) on the frequency and latency of a variety of cancers was examined. As compared to unexposed mice that spontaneously developed either lymphomas, hemangiosarcomas, spinal osteosarcomas, or undifferentiated sarcomas induced by physical injury, an exposure of 7-8 week old Trp53 +/- mice to either 10 or 100 mGy had no significant effect on tumor frequency, indicating no effect on tumor initiation. However, the 10 mGy exposure increased the mean tumor latency of all spontaneous cancers, as well as the cancers initiated by physical injury in these cancer prone mice. This result indicates that the main in vivo effect of a single low-dose, low dose rate exposure is reduced tumor risk resulting from a reduction in the rate at which initiated cells become genomicallly unstable. The protective effect of this adaptive response lasted for the entire lifespan of all the animals that developed these tumors, effectively restoring a portion of the mean loss of lifespan attributed to Trp53 heterozygosity in the absence of radiation exposure. Increasing the dose 10 fold to 100 mGy produced variable results, increasing risk (decreased latency) for some tumors but increasing latency for other tumors, indicating that this higher dose was in a transition zone between reduced and increased risk.

KEYWORDS: Low dose, Trp53, Spontaneous cancer, Adaption