Independent validation of candidate genes identified after a whole genome screening on Mayak workers exposed to prolonged occupational radiation.

Abstract

We evaluated gene expression in the peripheral blood of Mayak workers in relationship to occupational chronic exposure to identify permanent post-exposure signatures. The Mayak workers had experienced either a combined exposure to incorporated (239)Pu and external gamma rays (n = 82) or exposure to external gamma rays (n = 18). Fifty unexposed individuals served as controls. Peripheral blood was collected and then the RNA was isolated, converting it into cDNA and stored at -20°C. In a previous study at stage I, we screened the mRNA and microRNA transcriptome using 40 of the 150 samples and identified 95 mRNAs and 45 microRNAs. In stage II of this study, we now validated our 140 candidate genes using the qRT-PCR technique for the remaining 92 blood samples (18 samples were lost due to methodological reasons). We analyzed associations of normalized gene expression values in linear models separately for both exposure types (continuous and categorical scales) and adjusted for exposure age as well as stratified by gender. After further adjustment for confounders such as chronic non-cancer diseases or age at biosampling, mostly binary (on/off) dose-to-gene relationships were found for 15 mRNAs and 15 microRNAs, of which 8 mRNAs and 6 microRNAs remained significant after Bonferroni correction. Almost all of them were associated with plutonium incorporation and gender. Our study provides mRNA and microRNA gene expression changes dependent on the exposure type and gender, which occur and seem to persist after chronic radiation exposures supporting the concept of permanent post-exposure signatures.