Candidate protein biodosimeters of human exposure to ionizing radiation

Abstract

Purpose: To conduct a literature review of candidate protein biomarkers for individual radiation biodosimetry of exposure to ionizing radiation.

Materials and methods: Reviewed ∼300 publications (1973 – April 2006) that reported protein effects in mammalian systems after either in vivo or in vitro radiation exposure.

Results: We found 261 radiation-responsive proteins including 173 human proteins. Most of the studies used high doses of ionizing radiation (>4 Gy) and had no information on dose- or time-responses. The majority of the proteins showed increased amounts or changes in phosphorylation states within 24 h after exposure (range: 1.5- to 10-fold). Of the 47 proteins that are responsive at doses of 1 Gy and below, 6 showed phosphorylation changes at doses below 10 cGy. Proteins were assigned to 9 groups based on consistency of response across species, dose- and time-response information and known role in the radiation damage response.

Conclusions: ATM (Ataxia telengiectasia mutated), H2AX (histone 2AX), CDKN1A (Cyclin-dependent kinase inhibitor 1A), and TP53 (tumor protein 53) are top candidate radiation protein biomarkers. Furthermore, we recommend a panel of protein biomarkers, each with different dose and time optima, to improve individual radiation biodosimetry for discriminating between low-, moderate-, and high-dose exposures. Our findings have applications for early triage and follow-up medical assessments.

Keywords:

• Radiation response
• blood
• skin
• fibroblasts

Notes

Since our review of the literature was completed, the study of Yang et al. was published in the May 2006 issue of the Journal of Proteome Research (5, 1252 – 1260) describing the phosphoproteome prolifing of human skin fibroblast cells after exposure to either 2 or 400 cGy.