Project description:Introduction Iodine-131 (131I) is frequently used in nuclear medicine. Unbound or released 131I accumulate in the thyroid gland and may be detrimental to normal thyroid function. The aim of the present study was to identify biomarkers for 131I exposure in rat thyroid tissue and to assess the effect on thyroid function. Methods Thirty six male Sprague Dawley rats were i.v. injected with 150 Âµl saline solution containing 9.0, 88, 170, 260, 340, 760, 1300, or 4700 kBq (group A-H) 131I, or mock-treated with 150 Âµl saline solution only, and killed at 24 h after injection. Total RNA was extracted from individual thyroid tissue samples thyroids and mRNA levels were determined with the Agilent microarray platform. Results Estimated absorbed doses in treatment groups A-H was 0.0058, 0.057, 0.11, 0.17, 0.22, 0.5 Gy, 0.8 Gy, and 3 Gy. Totally, 429 transcripts were identified with a fold change fold change â¥ 1.5 and adjusted p-value â¤ 0.01. A trend with downregulation of thyroid hormone biosynthesis associated genes (e.g. thyroglobulin, thyroid peroxidase, the sodium-iodine symporter) was identified, but only statistically significant after 0.0058 and 0.22 Gy. Three transcripts coding for isoform 1 of the DBP protein showed a pattern with monotonous decrease in downregulation with absorbed dose between 0.0058-0.22 Gy. Changes in Dbp expression were not statistically significant between 0.5-3 Gy. However, a trend with downregulation at 0.5 and 0.8 Gy and upregulation and 3 Gy was identified. Previously, 131I (0.85-17 Gy) and 211At (0.023-32 Gy) exposure resulted in upregulation of Dbp in mice thyroid tissue 24 h after administrations. Additionally, a monotonous decrease in Dbp downregulation has been identified of in mouse kidney tissue at 8 and 12 months after 177Lu-octreotate administrations. Conclusion Conclusively, the Dbp gene is a promising candidate biomarker gene for exposure to 131I and possibly other internal radiation emitters. Further studies should be performed to establish how Dbp expression vary with dose-rate, absorbed dose, time after administration, different radiation qualities, and the function of Dbp. Total RNA was isolated from fresh-frozen individual thyroid tissue samples (Sprague Dawley rats). Each sample was run once. Four rats received the same treatment. Control samples (from non-irradiated rats) are included.

Project description:Background: The effects of dose-rate and its implications on radiation biodosimetry methods are not well studied in the context of large-scale radiological scenarios. There are significant health risks to individuals exposed to an acute dose in such an event, but the most realistic scenario would be a combination of exposure to both high and low dose-rates, from both external and internal radioactivity. It is important therefore, to understand the biological response to prolonged exposure; and further, discover biomarkers that can be used to estimate the extent of damage from low-dose rate exposure and propose appropriate clinical treatment. Methods: We irradiated human whole blood ex vivo to three doses, 0.56 Gy, 2.25 Gy and 4.45 Gy, using two dose rates: 1.1Gy/min and 3.1mGy/min. After 24 hours, we isolated RNA from blood cells and hybridized these to Agilent Whole Human genome microarrays. We validated the microarray results using qRT-PCR. Results: Microarray results showed that there were 454 significantly differentially expressed genes after prolonged exposure to all doses. After acute exposure, 598 genes were differentially expressed to all doses combined. Gene ontology terms enriched in both sets of genes were related to immune processes and B cell mediated immunity. Genes responding to acute exposure was also enriched in functions related to natural killer cell activation and cell-to-cell signaling. As expected, p53 pathway was found to be significantly enriched at all doses and by both dose-rates of radiation. Prediction algorithms were able to distinguish between low dose-rate and acute exposures, on the basis of a group of genes. These maybe candidates for preliminary testing as markers for differences in gene expression based on dose-rate. Radiation induced gene expression was measured in ex vivo irradiated human blood, at the 24hr time point after irradiation. Doses (0.56 Gy, 2.2 Gy and 4.45 Gy) were delivered by two dose rates, acute dose rate of 1Gy/min and low dose rate of 3.1 mGy/min.

Project description:Introduction Iodine-131 (131I) is frequently used in nuclear medicine. Unbound or released 131I accumulate in the thyroid gland and may be detrimental to normal thyroid function. The aim of the present study was to identify biomarkers for 131I exposure in rat thyroid tissue and to assess the effect on thyroid function. Methods Thirty six male Sprague Dawley rats were i.v. injected with 150 µl saline solution containing 9.0, 88, 170, 260, 340, 760, 1300, or 4700 kBq (group A-H) 131I, or mock-treated with 150 µl saline solution only, and killed at 24 h after injection. Total RNA was extracted from individual thyroid tissue samples thyroids and mRNA levels were determined with the Agilent microarray platform. Results Estimated absorbed doses in treatment groups A-H was 0.0058, 0.057, 0.11, 0.17, 0.22, 0.5 Gy, 0.8 Gy, and 3 Gy. Totally, 429 transcripts were identified with a fold change fold change ≥ 1.5 and adjusted p-value ≤ 0.01. A trend with downregulation of thyroid hormone biosynthesis associated genes (e.g. thyroglobulin, thyroid peroxidase, the sodium-iodine symporter) was identified, but only statistically significant after 0.0058 and 0.22 Gy. Three transcripts coding for isoform 1 of the DBP protein showed a pattern with monotonous decrease in downregulation with absorbed dose between 0.0058-0.22 Gy. Changes in Dbp expression were not statistically significant between 0.5-3 Gy. However, a trend with downregulation at 0.5 and 0.8 Gy and upregulation and 3 Gy was identified. Previously, 131I (0.85-17 Gy) and 211At (0.023-32 Gy) exposure resulted in upregulation of Dbp in mice thyroid tissue 24 h after administrations. Additionally, a monotonous decrease in Dbp downregulation has been identified of in mouse kidney tissue at 8 and 12 months after 177Lu-octreotate administrations. Conclusion Conclusively, the Dbp gene is a promising candidate biomarker gene for exposure to 131I and possibly other internal radiation emitters. Further studies should be performed to establish how Dbp expression vary with dose-rate, absorbed dose, time after administration, different radiation qualities, and the function of Dbp.

Project description:Measuring global gene expression using cDNA or oligonucleotide microarrays is an effective approach to understanding the complex mechanisms of the effects of radiation. However, few studies have been carried out that investigate gene expression in vivo after prolonged exposure to low-dose-rate radiation. In this study, C57BL/6J mice were continuously irradiated with ?-rays for 485 days at dose-rates of 0.032 – 13 ?Gy/min. Gene expression profiles in the kidney and testis from irradiated and unirradiated mice were analyzed, and differentially expressed genes were identified. A combination of pathway analysis and hierarchical clustering of differentially expressed genes revealed that expression of genes involved in mitochondrial oxidative phosphorylation was elevated in the kidney after irradiation at the dose-rates of 0.65 ?Gy/min and 13 ?Gy/min. Expression of cell cycle-associated genes was not profoundly modulated in the kidney, in contrast to the response to acute irradiation, suggesting a threshold in the dose-rate for modulation of the expression of cell cycle-related genes in vivo following exposure to radiation. We demonstrated that changes to the gene expression profile in the testis were largely different from those in the kidney. The Gene Ontology categories “DNA metabolism”, “response to DNA damage” and “DNA replication” overlapped significantly with the clusters of genes whose expression decreased with an increase in the dose-rate to the testis. These observations provide a fundamental insight into the organ-specific responses to low-dose-rate radiation. Key Words: kidney, low-dose-rate, radiation, microarray, mitochondrial oxidative phosphorylation, testis 3 biological replicates for each experimental group were analysed. GSE14290_Kidney_raw_data.csv contains the raw data for GSM357146, GSM357425, GSM357426, GSM357452 to GSM357460. GSE14290_Testis_raw_data.csv contains the raw data for GSM357471 to GSM357482. In these files, the sample identifiers are included in the column headers.

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