Identification of potential mRNA biomarkers in peripheral blood lymphocytes for human exposure to ionizing radiation

Since early in the Atomic Age, biological indicators of radiation exposure have been sought, but currently available methods are not entirely satisfac tory. Using cDNA microarray hybridization to discover new potential biomark ers, we have identified genes expressed at increased levels in human periph eral blood lymphocytes after ex vivo irradiation. We recently used this tec hnique to identify a large set of ionizing radiation-responsive genes in a human cell line (Oncogene 18, 3666-3672, 1999). The present set of radiatio n markers in peripheral blood lymphocytes was identified 24 h after treatme nt, and while the magnitude of mRNA induction generally decreased over time , many markers were still significantly elevated up to 72 h after irradiati on. In all donors, the most highly responsive gene identified was DDB2, whi ch codes for the p48 subunit of XPE, a protein known to play a crucial role in repair of ultraviolet (UV) radiation damage in DNA. Induction of DDB2, CDKN1A (also known as CIP1/WAF1) and XPC showed a linear dose-response rela tionship between 0.2 and 2 Gy at 24 and 48 h after irradiation, with less l inearity at earlier or later times. These results suggest that relative lev els of gene expression in peripheral blood cells may provide estimates of e nvironmental radiation exposures. (C) 2000 by Radiation Research Society.