Project description:Thyroid gland is among the most sensitive organs to ionizing radiation. Whether low-dose radiation-induced papillary thyroid cancer (PTC) differs from sporadic PTC is yet unknown. We used microarrays to identify gene signature of radiation-induced papillary thyroid carcinomas
Project description:Recent observations show that the single-cell response of p53 to ionizing radiation (IR) is “digital” in that it is the number of oscillations rather than the amplitude of p53 that shows dependence on the radiation dose. We present a model of this phenomenon. In our model, double-strand break (DSB) sites induced by IR interact with a limiting pool of DNA repair proteins, forming DSB–protein complexes at DNA damage foci. The persisting complexes are sensed by ataxia telangiectasia mutated (ATM), a protein kinase that activates p53 once it is phosphorylated by DNA damage. The ATM-sensing module switches on or off the downstream p53 oscillator, consisting of a feedback loop formed by p53 and its negative regulator, Mdm2. In agreement with experiments, our simulations show that by assuming stochasticity in the initial number of DSBs and the DNA repair process, p53 and Mdm2 exhibit a coordinated oscillatory dynamics upon IR stimulation in single cells, with a stochastic number of oscillations whose mean increases with IR dose. The damped oscillations previously observed in cell populations can be explained as the aggregate behavior of single cell
Project description:Genetic differences in transcript responses to low-dose ionizing radiation identify tissue functions associated with breast cancer susceptibility.
Project description:The immune system illustrates the challenges of assigning risk to low dose radiation (LDR) exposure in a population. While high radiation doses clearly suppress immune function, a number of studies have shown that LDR affects immune cell subpopulations in ways that could be beneficial. In the intact organism, defining the consequences of LDR is further complicated by the impact of genetic background, particularly in systems such as the immune system for which both radiosensitivity and genetic effects are profound. We employed a systems genetics approach to test for heritable differences in LDR responses. Mice from 39 BXD recombinant inbred (RI) strains were exposed to 10cGy gamma radiation to determine effects on immune function and oxidative stress 48h after irradiation. LDR significantly enhanced neutrophil phagocytosis in a manner that was independent of genetic background. In contrast, genetic background significantly impacted LDR-induced changes in spleen superoxide dismutase activity. Transcriptome data from spleens of the BXD parental strains highlighted the impact of genetic background on LDR responses and also indicate that genetic variation in radiosensitivity is further unmasked at low radiation doses. Taken together, these data highlight the need to consider genetic variation when assessing LDR outcomes. Adult C57BL/6J and DBA/2J mice (10 weeks old) were exposed to low dose (10cGy) or high dose (1Gy) gamma radiation. Mice were sacrificed 24h after radiation or sham exposure & spleens were harvested for transcriptomic analysis.
Project description:Human embryonic stem cells (hESCs) present a novel platform for in vitro investigation of the early embryonic cellular response to ionizing radiation. Thus far, no study has analyzed the genome-wide transcriptional response to ionizing radiation in hESCs. In this study, we use Agilent microarrays to analyze the global gene expression changes in H9 hESCs after low (0.4 Gy), medium (2 Gy), and high (4 Gy) dose irradiation.
