Gene expression responses in lymphoblastoid cells after radiation exposure

Individual differences in response to radiation are well known, but the mol ecular basis for these differences is not well understood, and molecular in dicators that are useful in assessing individual variation are lacking. Cel ls from patients developing unexpected radiation responses have occasionall y 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 radi ation response. We hypothesize that much of the variation in the response t o radiation is due to differences in the genes that respond to radiation ex posure, and that changes in gene expression may serve as surrogate markers of individual response. As a first step in developing a selection of suitab le markers of gene expression, we used cDNA microarrays to identify genes t hat were altered in expression in lymphoblastoid cells 4 h after exposure t o 1 Gy X rays. We found changes in gene expression ranging from a 10-fold r epression to a 12-fold induction. Some of the responsive genes have been no ted previously in other cell types, whereas others are reported for the fir st time. Using these data, we are beginning to characterize the range of st ructural, temporal and functional variations in the responsive genes. The r esults of this work will assist in developing response markers both for pre screening for sensitive individuals and for risk assessment. (C) 2001 by Ra diation Research Society.