Breath biomarkers of total body irradiation in non-human primates

Abstract

Background. Radiation exposure causes oxidative stress, eliciting production of metabolites that are exhaled in the breath as volatile organic compounds (VOCs). We evaluated breath VOCs as potential biomarkers for use in radiation biodosimetry. Methods. Five anesthetized non-human primates receive total body irradiation (TBI) of three daily fractions of 120 cGy per day for three days, resulting in a cumulative dose of 10.8 Gy. Breath samples were collected prior to irradiation and after each radiation fraction, and analyzed with gas chromatography mass spectrometry. Results. TBI elicited a prompt and statistically significant increase in the abundance of several hundred VOCs in the breath, including some that were increased more than five-fold, with100% sensitivity and 100% specificity for radiation exposure. The most significant breath VOC biomarkers of radiation mainly comprised straight-chain n-alkanes (e.g. hexane), as well as methylated alkanes (e.g. 3-methyl-pentane) and alkane derivatives (e.g. 2-butyl-1-octanol), consistent with metabolic products of oxidative stress. An unidentified breath VOC biomarker increased more than ten-fold following TBI, and rose linearly with the total cumulative dose of radiation (R 2 = 0.92). Conclusions. TBI of non-human primates elicited increased production of breath VOCs consistent with increased oxidative stress. These findings provide a rational basis for further evaluation of breath VOC biomarkers in human radiation biodosimetry.