Deregulated Pathways in a Human Lymphoblastoid Cell Line after Low Doses of Gamma Irradiation

摘要

Transcriptome analysis now permits the exploration of the effects of low doses of radiation and potentially can provide a global view of radiation responsive pathways. The present work focuses on the comparison of the variation of gene expression with regard to the cellular response induced after either 0.02 or 2 Gy gamma radiation exposure of a human lymphoblastoid cell line. It was observed that: a) a lower number of genes was deregulated after 0.02 compared to 2 Gy, b) some genes were specifically deregulated according to the dose while others were similarly deregulated whatever the dose, c) functional grouping of all ionizing radiations responsive genes after high or low doses showed that the pathways most frequently involved are the same and correspond to signal transducu'on, cytoskeleton, protein metabolism catabolism and modification, intracellular trafficking and transcription factors, d) genes specifically deregulated at the high dose did not present specificity regarding their functional grouping compared to pathways described above while genes specifically deregulated after 0.02 Gy were mainly involved in signal transducn'on, cytoskeleton, stress response, ionic transport and channel and e) after both doses, responsive genes related to cell survival and death were in good agreement with data obtained on cell survival and death. Overall, the results support the hypothesis that low doses of ionizing radiation lead to a typical stress-induced translation inhibition and UNA processing alteration. The utility ofDNA microarray to obtain an integrated view of the radiation response is emphasized and the need for further efforts to explore the effects of low doses of radiation is underlined. The results suggest that part of the response at low doses cannot be predicted by extrapolation from data obtained at high doses.