EVALUATION OF THE RESPONSE TO LOW DOSE IONIZING RADIATION BY GENE EXPRESSION PROFILE

The use of radioactive materials in medicine, power generation and industry is a considerable concern for occupational exposure, since human health risks from low doses of radiation are still debated. The functional genomics seems to be the best approach to study the complexity of response to ionizing irradiation (IR). We performed in vitro and in vivo studies to verify the effects of the exposure to low doses IR on gene profiles. BALB/c 3T3 cells were exposed to a 137Cs radiation source and allowed to repair potentially lethal damages for 20 h. Cell survival and IR-induced transformation was determined. Gene expression in irradiated and control cells was evaluated by microarray technology. A dose-related reduction in cloning efficiency was induced by 1.5-6 Gy exposure. Cell proliferation was induced at lower doses, thus suggesting a hormetic effect. A study was carried out in 28 workers that were exposed to low-LET ionizing radiations at a large health care facility. We compared the expression profile of their peripheral blood lymphocytes (PBMC) with a reference sample of non-exposed people, working at the same place. A balanced block design was used. Labeled c-RNA was synthetised from PBMC m-RNA, purified and applied the oligonucleotide slide (Human1A oligo microarray, G4110A) according to the Agilent 60-mer oligo microarray processing protocol. Slides were scanned in Agilent dual laser Microarray Scanner. The scanned image was analysed by bioinformatics techniques. By this approach, 270 genes were identified, which were correlated to the occupational IR exposure, including chromatin assembled genes and genes involved in apoptosis, DNA repair and response to stress. This IR transcriptional fingerprint could add information to the current models of risk for chronic low dose exposure.