Profile of Gene Expression Induced By Ionising Radiation in Different Human Cell Types

This study deals with the transcriptional alterations induced by radiation in human transformed and non-transformed cells. Profiles of gene expression obtained with cDNA microarrays were regarded as steps to characterize the general response to ionizing radiation and, possibly also, differentiating the response between transformed and nontransformed cells. Possible implications of such research include the development of radiosensitizing (to maximize the effect of radiotherapeutic irradiation) and of radioprotecting strategies. Transcriptional profiles were investigated in transformed (Jurkat, HL60) and non-transformed (freshly isolated lymphocyte subpopulations) cells of hematopoietic origin. Also, because HeLa carcinoma-derived cells expressing human papilloma virus (HPV) 18 derived E2 protein represent a reliable model to study the p53 pathway, which is normally activated in response to radiation, molecular profiles were obtained to characterize this pathway in these cells. The study is divided into four parts: • Cellular and molecular effects induced by acute X-ray irradiation in transformed and non-transformed cells • Unraveling transcription profiles in the response to irradiation • Reactivation of the p53 pathway in p53-negative cells with a recombinant adenovirus vector expressing the E2 protein from HPV18 • Study of the interference between the effects of E2 protein expression and X-ray irradiation in transformed cells