Early Biomarkers Associated with P53 Signaling for Acute Radiation Injury

Abstract

Background: Rapid and accurate high-throughput estimation of radiation dose aims to help medical rescue in nuclear radiation accident. However, current methods of dose estimation are still lacking of speedy or accuracy. P53 signaling pathway plays an important role in DNA damage repair and cell apoptosis induced by ionizing radiation. The changes of radiation-induced P53 related genes in the early stage of ionizing radiation should compensate for the deficiency of lymphocyte decline and γ-H2AX analysis as novel biomarkers of radiation damage. Methods: Bioinformatic analysis was performed on previous data to find candidate genes from human peripheral blood irradiated in vitro. The radiation sensitivity and baseline levels of candidate genes were verified. The approximate threshold for guiding medical treatment was estimated for each gene, and four genes were combined to construct an effectively early dose estimation model of radiation.Results: Four p53-related genes, DDB2, AEN, TRIAP1 and TRAF4, were screened and verified their significant radiosensitivity. Their expressions were stable without gender or age difference in healthy population, but significantly up-regulated by radiation, with time specificity and dose dependence in 2h-24h after irradiation. Further studies showed these genes can be used as indicators for early medical treatment in acute radiation injury. The effective combination of the four genes could achieve a more accurate dose assessment and injury classification for large-scale wounded patients within 24 hours post exposure.Conclusions: This is the first time to investigate the potential biomarkers of ionizing radiation by systematic study. The effective combination of the four genes provides a new model for dose estimation and injury classification of a large number of exposed population in acute nuclear accidents, and also provides a new idea and method.