Abstract
Abstract Radiotherapy is an efficient method of treating cancer. Several decades of clinical observation in patients treated with radiation/ radiomimetic drugs has, however, revealed undesirable consequences to the normal tissue. Ionizing radiation induced normal tissue injury manifests through symptoms such as hair loss, skin regeneration defects, erosion of intestinal epithelium, hematopoietic anomalies, diminished sperm counts, infertility, neuro-cognitive impairments etc. The phenomenon of “stem cell drop-out” can be attributed as the underlying cause for these side effects. However, insufficient research has been conducted for investigating the relative radiosensitivity of undifferentiated stem/ progenitor cells compared to their differentiated progenies and the underlying molecular mechanisms of this differential radiation response (DNA damage response and IR induced apoptotic response). We demonstrate stem cell specific apoptosis and hypersensitivity to low dose IR in various stem cell niches in vivo. Further, this stem cell hypersensitivity observed in the mouse tissue niches, is recapitulated in multiple primary cell culture models of undifferentiated stem cells and isogenic differentiated cells grown in appropriate stem cell culture/ differentiation conditions. Cell cycle parameters, checkpoint response and radiosensitive phases of these cells have been studied. Towards characterizing the novel associations between cellular differentiation, DNA damage response and apoptotic response, we have studied alterations in transcription profiles of stem and isogenic differentiated cells with and without radiation. Our investigation has uncovered transcriptional induction and suppression of genes that are unique to differentiation states. Results of our studies will be presented. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4350. doi:1538-7445.AM2012-4350
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