Early Biomarkers Associated with P53 Signaling for Acute Radiation Injury.

Weihong Li,Shixiang Zhou,Meng Jia,Xiaoxin Li,Yaqiong Li,Pingkun Zhou,Zhidong Wang,Qi Wang,Lin Li,Zhenhua Qi

doi:10.3390/life12010099

Abstract

Accurate dose assessment within 1 day or even 12 h after exposure through current methods of dose estimation remains a challenge, in response to a large number of casualties caused by nuclear or radiation accidents. 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. Bioinformatic analysis was performed on previous data to find candidate genes from human peripheral blood irradiated in vitro. The expression levels of candidate genes were detected by RT-PCR. The expressions of screened DDB2, AEN, TRIAP1, and TRAF4 were stable in healthy population, but significantly up-regulated by radiation, with time specificity and dose dependence in 2–24 h after irradiation. They are early indicators for medical treatment in acute radiation injury. Their effective combination could achieve a more accurate dose assessment for large-scale wounded patients within 24 h post exposure. The effective combination of p53-related genes DDB2, AEN, TRIAP1, and TRAF4 is a novel biodosimetry for a large number of people exposed to acute nuclear accidents.

Highlights

Estimation of radiation dose and classification of damage for large numbers of wounded in the early stage of nuclear accidents will effectively guide the application of treatment plans and improve the capacity of treatment and rescue [1,2,3].The 0.5 Gy irradiation will cause a slight decline of peripheral blood lymphocytes counts and recover spontaneously
Lymphocyte chromosome aberration analysis is considered as the “gold standard” for biological dose estimation of radiation for its higher specificity and accuracy
Ionizing radiation causes a significant decline in peripheral blood lymphocytes, and the degree is dramatically related to the dose

Summary

Introduction

Estimation of radiation dose and classification of damage for large numbers of wounded in the early stage of nuclear accidents will effectively guide the application of treatment plans and improve the capacity of treatment and rescue [1,2,3].The 0.5 Gy irradiation will cause a slight decline of peripheral blood lymphocytes counts and recover spontaneously. Patients irradiated 10 Gy will suffer multi-organ syndrome (MODS) which may result in multi-organ failure (MOF) which is irreversible [4,5,6]. Lymphocyte chromosome aberration analysis is considered as the “gold standard” for biological dose estimation of radiation for its higher specificity and accuracy. The lymphocyte count analysis within 12 to 48 h after irradiation is used for classification and preliminary dose estimation of patients with radiation injury. Peripheral blood lymphocyte count analysis can be used for triage in large number of patients, and the accurate dose can only be estimated by chromosome aberration analysis. According to the technical characteristics of both methods, it is impossible to achieve patient classification and accurate dose assessment only by lymphocyte count analysis or chromosome aberration analysis in the early post-accident period

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