Characterization of gene expression profiles at low and very low doses of ionizing radiation.

The aim of the present study is to analyse by microarray techniques how gene expression is modulated after exposure to low and very low doses of ionizing radiation, to evaluate if the pattern of gene expression shows dose dependence, and to search for putative regulatory mechanisms behind the observed gene-expression modifications. For this, whole blood samples from five healthy donors were exposed in six doses between 5 and 500mGy. Total RNA extraction from CD4(+) lymphocytes was done at four different post-irradiation times. After mRNA amplification, aRNAs were hybridized on DNA microarrays. The results indicated that up-regulation was twice than down-regulation. Surprisingly, the number of modulated genes does not seem to change drastically with dose, even at the lowest dose of 5mGy. Clustering analysis revealed seven gene expression clusters with different dose dependence profiles. The functional analysis showed that the genes which increased their expression with the dose were related to p53 pathway and DNA damage response. This could be observed from 25mGy, but became very clear at doses equal or greater than 100mGy. On the other hand, genes with a constant modulation of their expression in all the tested doses were related to cellular respiration, ATP metabolic process and chromatin organization. These latter molecular mechanisms seem to be triggered at very low doses (5-25mGy). In silico promoter analysis seems to confirm the implication of transcription factors related to the pathways mentioned above.