Improvement of Radiation Dose Assessment Using Multiple-Protein Expression and Hematological Profiles N.I. Ossetrova , 1 G.D. Ledney, 1 A.M. Farese, 2 T.J. MacVittie, 2 D.J. Sandgren, 1 S. Gallego, 1 and W.F. Blakely 1 1 Armed Forces Radiobiology Research Institute (AFRRI) 8901 Wisconsin Ave., Bethesda, MD, 20889-5603 USA 2 Marlene and Steward Greenebaum Cancer Center Bressler Research Building, Room 7-039 University of Maryland-Baltimore 655 West Baltimore Street, Baltimore, MD 21201 USA e-mail: ossetrova@afrri.usuhs.mil There is a present need to rapidly identify severely irradiated individuals that require prompt medical treatment in mass-casualty incidents, as well as to distinguish exposed vs. non-exposed individuals (Blakely et al. 2005). Early treatment of populations exposed to ionizing radiation (MacVittie et al. 2005; Waselenko et al. 2004) requires accurate and rapid biodosimetry with a precision as high as possible to determine an individual’s exposure level and risk for morbidity and mortality. The early medical- management situation in the Chernobyl nuclear power accident was made difficult because for several days after the incident the doses to individuals were not known with precision (Guskova et al. 2001). The development of accurate methods for rapid individual dose assessment possesses some challenges. A ma- jor source of uncertainty is individual variability in radiation response. Hematological biomarkers of exposure to ionizing radiation are well characterized and used in medical management of radiological casualties (Dainiak et al. 2003). Measurements of lymphocyte depletion ki- netics (Baranov et al. 1995; Goanz et al. 1997) and time- and dose-dependent changes in neutrophil cell numbers observed after irradiation (Fliedner et al. 2001) provide clinical information soon after exposure. However, because of large variation in lymphocyte and neutrophil counts among normal individuals, it necessitates repeated measurements over a prolonged period. Normalization of the inter-individual varia- tions in the ratio of neutrophils to lymphocytes has been evaluated and used along with lymphocyte deple- tion kinetics to get an enhanced discrimination index of radiation exposure (Zlang et al. 2004; Blakely et al. 2007). Proteomics is an area offering hope for potential new biological indicators of radiation exposure. Radia- tion responsive proteins have considerable potential as biodosimeters. Evaluation of specific changes in radiation-induced protein profiles will likely identify sentinel responsive targets and hence provide a prac- tical means to measure tissue- and organ-systems radiation injury. A proteomic approach may evaluate an individual’s responses to radiation exposure, since the individual’s characteristic and dynamic protein expression profile will reflect their unique biological system. Tissue specific protein biomarkers detected in peripheral blood can provide diagnostic information of organ specific radiation injury. Proteomic analyses may also be applicable for triage purposes, providing rapid estimation of individual exposure doses (Marchetti et al. 2006). The advancement in this type of research might also provide a powerful tool for the accurate assessment of an individual’s radiation risk response, hence, determine appropriate pre- as well as post-exposure interventions. PB-Rad-Injury 2008 Workshop Page 1 of 2