ABSTRACT: Genetic differences in transcript responses to low-dose ionizing radiation identify tissue functions associated with breast cancer susceptibility.
Project description:Skin is usually exposed during human exposures to ionizing radiation, however there are few experiments that evaluate the radiation responsiveness of the cells of the epidermis (keratinocytes) and those of the dermis (fibroblasts) in the same studies. We evaluated the transcriptional responses of quiesent primary keratinocytes and fibroblasts from the same individual and compared them with quiescent keratinocytes and fibroblasts that were immortalized by human telomerase (hTert). The primary transcriptional responses to 10-500 cGy ionizing radiation were p53-mediated responses; however, we did identify distinct responses between the keratinocytes and the fibroblasts. Keywords: keratinocytes and fibroblasts - dose response to ionizing radiation
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:The ability to detect trace amounts of ionizing radiation is a paramount concern for chemical, biological, radiological, nuclear, and explosives (CBRNE) operations and observation of clandestine activities in the event of source relocation and contamination. Microbes respond to environmental stress such as fluctuations in pH and temperature, nutrient limited conditions, and oxidative stress with morphological and behavioral changes, and induced responses are known to persist after the stressor is removed. Innate responses to other external stressors like exposure to low-dose ionizing radiation could be measured and characterized by changes in gene expression and resulting transcriptional changes could by engineered into biosensors to monitor and discern the presence and type of radiation, respectively, in the environment. The current understanding of the biological and transcriptional responses of bacteria to various doses of ionizing radiation is minimal. The work in this study expands upon the findings in our previous study of the response of a model bacterium to low doses of ionizing radiation soil bacterium, Pseudomonas putida KT2440. Following exposure to an approximate absorbed dose rate of 9 mGy d-1 of a 239Pu, 3H, or 55Fe source, RNA-seq analysis revealed key changes in gene expression of P. putida of genes encoding membrane components, central carbon metabolism, DNA repair pathways, and motility. Several genes were differentially expressed genes in P. putida after exposure to multiple radionuclide sources. Moreover, other genes were uniquely differentially expressed by a single radionuclide source. These findings expand upon the limited understanding of the biological response to low doses of ionizing radiation and provide fundamental characterization required to develop discriminatory RNA-based biosensors.
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 To identify molecular differences between radiation-induced (Exposed to Chernobyl Radiation, ECR) and sporadic PTC, we investigated 65 childhood/young adult PTC samples using DNA microarray (Affymetrix, Human Genome U133 2.0 Plus). The PTC samples were from patients born either before (33 ECR cases) or at least 9 months after (32 non-ECR cases) the Chernobyl catastrophe. Multofactoral analyses were performed in order to define some additional factors that could have impact on the gene expression profile. Morover the microarray data were validated with the QPCR reaction and exon arrays.
Project description:Investigation of ATM-dependent and dose-dependent, or -independent, responses were examined in human lymphoblast cells 6 hr following exposure to either 1 or 5 Gy ionizing radiation. Human lymphoblast cells from "apparently healthy" individuals and individuals with Ataxia telangiectasia were exposed to 1 Gy or 5 Gy ionizing radiation. Gene expression responses 6 hr following IR were examined. Untreated samples were hybridized together with their matched treated samples.
Project description:Characterization of biological and chemical responses to ionizing radiation by various organisms is essential for potential applications in bioremediation, alternative modes of detecting nuclear material, and national security. Escherichia coli DH10β is an optimal system to study the microbial response to low-dose ionizing radiation at the transcriptional level because it is a well-characterized model bacterium and its responses to other environmental stressors, including those to higher radiation doses, have been elucidated in prior studies. In this study, RNA sequencing with downstream transcriptomic analysis (RNA-seq) was employed to characterize the global transcriptional response of stationary-phase E. coli subjected to Pu-239, H-3 (tritium), and Fe-55, at an approximate absorbed dose rate of 10 mGy day-1 for 1 day and 15 days. Differential expression analysis identified significant changes in gene expression of E. coli for both short- and long-term exposures. Radionuclide source exposure induced differential expression in E. coli of genes involved in biosynthesis pathways of nuclear envelope components, amino acids, and siderophores, transport systems such as ABC transporters and type II secretion proteins, and initiation of stress response and regulatory systems of temperature stress, the RpoS regulon, and oxidative stress. These findings provide a basic understanding of the relationship between low-dose exposure and biological effect of a model bacterium that is critical for applications in alternative nuclear material detection and bioremediation. IMPORTANCE Escherichia coli strain DH10β, a well-characterized model bacterium, was subjected to short-term (1-day) and long-term (15-day) exposures to three different in situ radiation sources comprised of radionuclides relevant to nuclear activities to induce a measurable and identifiable genetic response. We found E. coli had both common and unique responses to the three exposures studied, suggesting both dose rate- and radionuclide-specific effects. This study is the first to provide insights into the transcriptional response of a microorganism in short- and long-term exposure to continuous low-dose ionizing radiation with multiple in situ radionuclide sources and the first to examine microbial transcriptional response in stationary phase. Moreover, this work provides a basis for the development of biosensors and informing more robust dose-response relationships to support ecological risk assessment.