Project description:To explore the molecular signaling pathways underlying different dose-rate modes, the intestinal tissues of mice were utilized to perform transcriptome sequencing. The result revealed that low mean dose-rate and low instantaneous dose-rate irradiation (LL mode) and ultra-high mean dose-rate and ultra-high instantaneous dose-rate irradiation (HH mode) evoked differential signaling pathways. Compared with LL mode, the signaling pathways of immune response were activated by HH, whereas the signals of mitochondrial metabolism and biogenesis, biological oxidation, amino acid metabolism and biosynthesis were suppressed under HH mode.
Project description:We compared gene expression differences in the polytypic species complex Mus musculus (Mus musculus musculus, Mus musculus domesticus, Mus musculus castaneus and Mus musculus ssp) with that of Mus spretus via oligonucleotide microarrays representing more than 20,000 genes. Analysis of the results by two way ANOVA statistics suggests that the most genes with significant differences in expression levels among the subspecies are found in liver and kidney and the least in testis. This picture is different when one compares with Mus spretus, where the largest number of differences is found in testis. Keywords: multi-species comparison
Project description:To obtain more insight in the molecular effects of chronic low dose irradiation on endothelial cells, HUVEC were irradiated with low-dose rate irradiation (137Cs gamma source; 0, 1.4 and 4.1 mGy/h) for several weeks. At different time points (1, 3 and 6 weeks) cells were harvested for RNA extraction and hybridisation to Affymetrix GeneChip Human Gene 1.0 ST arrays.
Project description:We explored the microevolutionary trends of CTCF binding evolution by preforming ChIP-seq experiments in five closely related Mus strains, subspecies and species: Mus musculus domesticus, Mus musculus castaneus, Mus spretus, Mus caroli and Mus pahari. All experiments were performed in adult male liver samples in 3 biological replicates and with an input control set. Complementary RNA-seq data from this same study have been deposited in ArrayExpress under accession numebr E-MTAB-5768 ( https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-5768 ).
Project description:Caesium-137 (Cs-137) is one of the major radionuclides appearing in the natural environment after nuclear power plant accidents. However, the biological effects of low-dose internal irradiation with this radionuclide remain unclear. We developed an experimental model for studying low-dose internal irradiation using cultured human cells. The cells were incubated in the culture medium supplemented with unsealed Cs-137 chloride. We used the Monte Carlo simulation method for measuring internal irradiation because making direct measurements was not possible. The simulation revealed that 96.40%?99.70% of the internal irradiation involved ?-particles and other electrons. During the experiment, a gradual incorporation of Cs-137 in the cells, and the absorbed dose rate increased in a time-dependent manner. In addition, the number of ?-H2AX and 53BP1 nuclear foci in the cells increased by internal irradiation in a dose-dependent manner. Microarray analysis revealed time-dependent alterations in gene expression caused by the radiation. These results demonstrate that our experimental system can be useful in the investigation of the effects of low-dose internal irradiation.
Project description:The biomedical consequences of space radiation pose a significant concern for astronauts engaged in deep space. However, the effects of long-term low dose-rate exposures in space environments remain elusive. In this study, we simulated the space radiation environment by exposing human bronchial epithelial cells to low dose-rate (0.0067 Gy/day) α-particles, and continuously irradiated them multiple times to achieve cumulative total doses of 0.2 Gy, 0.4 Gy, and 0.5 Gy, respectively. At the same time, the cells were irradiated with the same total dose in a single exposure to investigate the potential of low dose-rate alpha particles to induce malignant transformation of human bronchial epithelial cells. A comprehensive suite of assays was employed to assess tumorigenic potential, including tumor formation in NOD/SCID mice, immunohistochemistry, CCK-8 proliferation assay, invasion assay, and the evaluation of multicellular spheroid formation during subsequent passages post-irradiation. Moreover, we dissected differential malignant mechanisms in tumor evolution ecosystem induced by the two distinct irradiation modes from systems biology views based on scRNA-seq technology. Our results showed that exposure to α-particles, whether through a single acute exposure or long-term low dose-rate exposures, induced the occurrence and development of tumors. Long-term low dose-rate exposures to α-particles increase the malignancy of induced tumors, but not the risk of carcinogenesis, compared to a single acute exposure with the same total dose. In addition, through scRNA-seq, we found that long-term low dose-rate exposures triggered more copy number variation (CNV) and epithelial-mesenchymal transition (EMT) events, and the activation of DNA damage repair pathways occurred significantly later than with a single acute exposure and involved more specific changes in cellular communication dynamics. In conclusion, our findings provide emerging yet convincing evidence that not only sheds light on why cells exposed to long-term low dose-rate exposures exhibit heightened malignancy, but also offers valuable insights into the genetic determinants driving tumor evolution and heterogeneity.
Project description:We compared gene expression differences in the polytypic species complex Mus musculus (Mus musculus musculus, Mus musculus domesticus, Mus musculus castaneus and Mus musculus ssp) with that of Mus spretus via oligonucleotide microarrays representing more than 20,000 genes. Analysis of the results by two way ANOVA statistics suggests that the most genes with significant differences in expression levels among the subspecies are found in liver and kidney and the least in testis. This picture is different when one compares with Mus spretus, where the largest number of differences is found in testis. The design we employed is a reference design. All tissues were hybridized against a pool of that same tissue from 9 C57BL6 mice. All mice were roughly 12 weeks of age. To control for biological variation, we have used several individual males from each sub-species. RNA was isolated from three different organs, namely brain, liver/kidney and testis.