Radiation Risk Prediction and Genetics: The Influence of the TP53 Gene in vivo

Abstract

Risk prediction and dose limits for human radiation exposure are based on the assumption that risk is proportional to total dose. However, there is concern about the appropriateness of those limits for people who may be genetically cancer prone. The TP53 gene product functions in regulatory pathways for DNA repair, cell cycle checkpoints and apoptosis, processes critical in determining ionizing radiation risk for both carcinogenesis and teratogenesis. Mice that are deficient in TP53 function are cancer prone. This review examines the influence of variations in TP53 gene activity on cancer and teratogenic risk in mice exposed to radiation in vivo, and compares those observations to the assumptions and predictions of radiation risk inherent in the existing system of radiation protection. Current assumptions concerning a linear response with dose, dose additivity, lack of thresholds and dose rate reduction factors all appear incorrect at low doses. TP53 functional variations can further modify radiation risk from either high or low doses, or risk from radiation exposures combined with other stresses, and those modifications can result in both quantitative and qualitative changes in risk.