Early molecular markers for retrospective biodosimetry and prediction of acute health effects

Radiation-induced biological changes occurring within hours and days after irradiation can be potentially used for either exposure reconstruction (retrospective dosimetry) or the prediction of consecutively occurring acute or chronic health effects. The advantage of molecular protein or gene expression (GE) (mRNA) marker lies in their capability for early (1-3 days after irradiation), high-throughput and point-of-care diagnosis, required for the prediction of the acute radiation syndrome (ARS) in radiological or nuclear scenarios. These molecular marker in most cases respond differently regarding exposure characteristics such as e.g. radiation quality, dose, dose rate and most importantly over time. Changes over time are in particular challenging and demand certain strategies to deal with. With this review, we provide an overview and will focus on already identified and used mRNA GE and protein markers of the peripheral blood related to the ARS. These molecules are examined in light of 'ideal' characteristics of a biomarkers (e.g. easy accessible, early response, signal persistency) and the validation degree. Finally, we present strategies on the use of these markers considering challenges as their variation over time and future developments regarding e.g. origin of samples, point of care and high-throughput diagnosis.