Gene expression profiles in human lymphocytes irradiated in vitro with low doses of gamma rays.

The molecular mechanisms underlying responses to low radiation doses are still unknown, especially in normal lymphocytes, despite the evidence suggesting specific changes that may characterize cellular responses. Our purpose was to analyze gene expression profiles by DNA microarrays in human lymphocytes after in vitro irradiation (10, 25 and 50 cGy) with gamma rays. A cytogenetic analysis was also carried out for different radiation doses. G 0 lymphocytes were irradiated and induced to proliferate for 48 h; then RNA samples were collected for gene expression analysis. ANOVA was applied to data obtained in four experiments with four healthy donors, followed by SAM analysis and hierarchical clustering. For 10, 25 and 50 cGy, the numbers of significantly (FDR <or= 0.05) modulated genes were 86, 130 and 142, respectively, and 25, 35 and 33 genes were exclusively modulated for each dose, respectively. We found CYP4X1, MAPK10 and ATF6 (10 cGy), DUSP16 and RAD51L1 (25 cGy), and RAD50, REV3L and DCLRE1A (50 cGy). A set of 34 significant genes was common for all doses; while SERPINB2 and C14orf104 were up-regulated, CREB3L2, DDX49, STK25 and XAB2 were down-regulated. Chromosome damage was significantly induced for doses >or=10 cGy (total aberrations) and >or=50 cGy (dicentrics/ rings). Therefore, low to moderate radiation doses induced qualitative and/or quantitative differences and similarities in transcript profiles, reflecting the type and extent of DNA lesions. The main biological processes associated with modulated genes were metabolism, stress response/DNA repair, cell growth/differentiation, and transcription regulation. The results indicate a potential risk to humans regarding the development of genetic instability and acquired diseases.