Abstract
Background: The effects of ionizing radiation on DNA integrity and functionality are well studied and reported. However, little is known about how irradiation affects large-scale nuclear architecture. We sought to investigate the latter using Chromosome Conformation Capture on Chip (4C) which assesses the spatial genomic organization around a locus of interest. Methods: U251 glioma cells were grown in standard media to 70% confluence, irradiated (6Gy) and harvested 6 and 24 hours after irradiation. We obtained all genomic loci in close physical proximity to an irradiation induced gene Alf1 on chromosome 6 as bait. 4C was performed in duplicate samples on control or irradiated cells, using custom NimbleGen microarrays that contained probes for all potential partner sites in the genome. Results: Alf1 locus was found to be engaged in multiple intra-chromosomal interactions with other regions in chromosome 6, and inter-chromosomal interactions with multiple areas in chromosomes 1,2,5,7,10 15 and 17 prior to irradiation. Irradiation induced changes in the Alf1 spatial environment as many of the contacts were lost, while additional interactions were induced. A partial recovery to the baseline nuclear architecture was evident 24 hrs after irradiation. Conclusions: Our preliminary results are intriguing and might suggest a new tool to investigate the effects of ionizing irradiation on nuclear high-order structure. A specific, time dependent post irradiation DNA architecture changes in tumor cells may correlate to the (and reproducible) levels of sensitivity to ionizing irradiation of different areas of the DNA in a specific tumor cell population.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 506.
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