Distinct effects of ionizing radiation on in vivo murine kidney and brain normal tissue gene expression.

PURPOSE: There is a growing awareness that radiation-induced normal tissue injury in late-responding organs, such as the brain, kidney, and lung, involves complex and dynamic responses between multiple cell types that not only lead to targeted cell death but also acute and chronic alterations in cell function. The specific genes involved in the acute and chronic responses of these late-responding normal tissues remain ill defined; understanding these changes is critical to understanding the mechanism of organ damage. As such, the aim of the present study was to identify candidate genes involved in the development of radiation injury in the murine kidney and brain using microarray analysis. EXPERIMENTAL DESIGN: A multimodality experimental approach combined with a comprehensive expression analysis was done to determine changes in normal murine tissue gene expression at 8 and 24 hours after irradiation. RESULTS: A comparison of the gene expression patterns in normal mouse kidney and brain was strikingly different. This observation was surprising because it has been long assumed that the changes in irradiation-induced gene expression in normal tissues are preprogrammed genetic changes that are not affected by tissue-specific origin. CONCLUSIONS: This study shows the potential of microarray analysis to identify gene expression changes in irradiated normal tissue cells and suggests how normal cells respond to the damaging effects of ionizing radiation is complex and markedly different in cells of differing origin.

Redox-sensitive signaling factors as a novel molecular targets for cancer therapy.

Tumor cells undergoing proliferation, de-differentiation and progression depend on a complex set of respiratory pathways to generate the necessary energy. The metabolites from these pathways produce significant oxidative stress and must be buffered to prevent permanent cell damage and cell death. It is now clear that, in order to cope with and defend against the detrimental effects of oxidative stress, a series of redox-sensitive, pro-survival signaling pathways and factors regulate a complex intracellular redox buffering network. This review develops the hypothesis that tumor cells use these redox-sensitive, pro-survival signaling pathways and factors - up-regulated due to increased tumor cell respiration - to evade the damaging and cytotoxic effects of specific anticancer agents. It further suggests that redox-sensitive, signaling factors may be potential novel targets for drug discovery.