Gene Expression Responses in Lymphoblastoid Cells after Radiation Exposure

Individual differences in response to radiation are well known, but the molecular basis for these differences is not well understood, and molecular indicators that are useful in assessing individual variation are lacking. Cells from patients developing unexpected radiation responses have occasionally been analyzed for rare genetic anomalies (such as alleles of the ATM gene), but few data exist on the long-term effects of genetic variation on radiation response. We hypothesize that much of the variation in the response to radiation is due to differences in the genes that respond to radiation exposure, and that changes in gene expression may serve as surrogate markers of individual response. As a first step in developing a selection of suitable markers of gene expression, we used cDNA microarrays to identify genes that were altered in expression in lymphoblastoid cells 4 h after exposure to 1 Gy X rays. We found changes in gene expression ranging from a 10-fold repression to a 12-fold induction. Some of the responsive genes have been noted previously in other cell types, whereas others are reported for the first time. Using these data, we are beginning to characterize the range of structural, temporal and functional variations in the responsive genes. The results of this work will assist in developing response markers both for prescreening for sensitive individuals and for risk assessment.