Mus musculus
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PROVIDER: PRJNA275859 | ENA |
REPOSITORIES: ENA
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Project description:Transcriptomic profiling of normal mouse thyroid tissue following 211At irradiation Introduction The cellular response to stimuli can be studied on different molecular levels, including gene expression regulation. RNA microarray is a high-throughput technique that enables comparison of genome-wide transcriptional status between samples. 211At-labeled radiopharmaceuticals are potentially useful for tumor therapy. Metabolically released 211At accumulates in the thyroid gland, which is one of the main critical organs for such therapy. The aim of this study was to determine the effect of absorbed dose, dose-rate, and time after 211At exposure on transcriptional expression in mouse thyroid gland. Method BALB/c mice were i.v. injected with 1.7, 7.5 or 100 kBq 211At. Animals injected with 1.7 kBq were killed after 1, 6, or 168 h with mean absorbed doses to thyroid of 0.023, 0.32, and 1.4 Gy, respectively. Animals injected with 7.5 and 100 kBq were killed after 6 and 1 h, respectively, resulting in mean absorbed doses to thyroid of 1.4 Gy. Animals were killed through cardiac puncture under anesthesia, and thyroids were removed and snap-frozen. Total RNA was extracted from pooled thyroid tissue samples and mRNA levels were determined with the Illumina RNA microarray platform. Nexus Expression 3.0 was used to identify differentially expressed transcripts (adjusted p-value <0.01, fold change >1.5) and enriched GO terms (p-value <0.05) between irradiated groups and controls. Results In total, 1232 differentially expressed transcripts were detected after 211At administration, demonstrating a profound effect on gene regulation. The number of regulated transcripts increased with higher initial dose-rate/absorbed dose when the exposure time was 1 or 6 h. However, the number of regulated transcripts decreased with mean absorbed dose/time after 1.7 kBq 211At administration. This suggests that initial dose-rate (thus injected activity) is an important parameter in radiation-induced responses. Furthermore, the regulation profiles of groups administered 1.7 kBq were similar. Few previously proposed radiation responsive genes were identified in the present study, but, e.g. Gadd45g and Cdkn1a were among the regulated genes identified in the present study. A response involving immunological processes was identified especially at 1, 6, and 168 h after 1.7 kBq administration (0.023, 0.32, 1.8 Gy). Conclusion The present study allowed a comprehensive assessment of how variations in exposure parameters affect transcriptional regulation. The regulation profiles were dependent on both absorbed dose and time after exposure, but, initial dose-rate was the most influential parameter. Functional annotation of regulated genes revealed exposure-specific effects on biological processes. Additionally, we have identified several recurrently regulated genes after 211At exposure that may play a role in how mouse thyroid tissue responds to 211At exposure. Introduction The cellular response to stimuli can be studied on different molecular levels, including gene expression regulation. RNA microarray is a high-throughput technique that enables comparison of genome-wide transcriptional status between samples. 211At-labeled radiopharmaceuticals are potentially useful for tumor therapy. Metabolically released 211At accumulates in the thyroid gland, which is one of the main critical organs for such therapy. The aim of this study was to determine the effect of absorbed dose, dose-rate, and time after 211At exposure on transcriptional expression in mouse thyroid gland. Method BALB/c mice were i.v. injected with 1.7, 7.5 or 100 kBq 211At. Animals injected with 1.7 kBq were killed after 1, 6, or 168 h with mean absorbed doses to thyroid of 0.023, 0.32, and 1.4 Gy, respectively. Animals injected with 7.5 and 100 kBq were killed after 6 and 1 h, respectively, resulting in mean absorbed doses to thyroid of 1.4 Gy. Animals were killed through cardiac puncture under anesthesia, and thyroids were removed and snap-frozen. Total RNA was extracted from pooled thyroid tissue samples and mRNA levels were determined with the Illumina RNA microarray platform. Nexus Expression 3.0 was used to identify differentially expressed transcripts (adjusted p-value <0.01, fold change >1.5) and enriched GO terms (p-value <0.05) between irradiated groups and controls. Results In total, 1232 differentially expressed transcripts were detected after 211At administration, demonstrating a profound effect on gene regulation. The number of regulated transcripts increased with higher initial dose-rate/absorbed dose when the exposure time was 1 or 6 h. However, the number of regulated transcripts decreased with mean absorbed dose/time after 1.7 kBq 211At administration. This suggests that initial dose-rate (thus injected activity) is an important parameter in radiation-induced responses. Furthermore, the regulation profiles of groups administered 1.7 kBq were similar. Few previously proposed radiation responsive genes were identified in the present study, but, e.g. Gadd45g and Cdkn1a were among the regulated genes identified in the present study. A response involving immunological processes was identified especially at 1, 6, and 168 h after 1.7 kBq administration (0.023, 0.32, 1.8 Gy). Conclusion The present study allowed a comprehensive assessment of how variations in exposure parameters affect transcriptional regulation. The regulation profiles were dependent on both absorbed dose and time after exposure, but, initial dose-rate was the most influential parameter. Functional annotation of regulated genes revealed exposure-specific effects on biological processes. Additionally, we have identified several recurrently regulated genes after 211At exposure that may play a role in how mouse thyroid tissue responds to 211At exposure. Total RNA was isolated from fresh-frozen tissue samples (Normal balb/c mouse thyroids)
2015-02-20 | E-GEOD-66089 | biostudies-arrayexpress
Project description:Transcriptomic profiling of normal mouse thyroid tissue following 211At irradiation Introduction The cellular response to stimuli can be studied on different molecular levels, including gene expression regulation. RNA microarray is a high-throughput technique that enables comparison of genome-wide transcriptional status between samples. 211At-labeled radiopharmaceuticals are potentially useful for tumor therapy. Metabolically released 211At accumulates in the thyroid gland, which is one of the main critical organs for such therapy. The aim of this study was to determine the effect of absorbed dose, dose-rate, and time after 211At exposure on transcriptional expression in mouse thyroid gland. Method BALB/c mice were i.v. injected with 1.7, 7.5 or 100 kBq 211At. Animals injected with 1.7 kBq were killed after 1, 6, or 168 h with mean absorbed doses to thyroid of 0.023, 0.32, and 1.4 Gy, respectively. Animals injected with 7.5 and 100 kBq were killed after 6 and 1 h, respectively, resulting in mean absorbed doses to thyroid of 1.4 Gy. Animals were killed through cardiac puncture under anesthesia, and thyroids were removed and snap-frozen. Total RNA was extracted from pooled thyroid tissue samples and mRNA levels were determined with the Illumina RNA microarray platform. Nexus Expression 3.0 was used to identify differentially expressed transcripts (adjusted p-value <0.01, fold change >1.5) and enriched GO terms (p-value <0.05) between irradiated groups and controls. Results In total, 1232 differentially expressed transcripts were detected after 211At administration, demonstrating a profound effect on gene regulation. The number of regulated transcripts increased with higher initial dose-rate/absorbed dose when the exposure time was 1 or 6 h. However, the number of regulated transcripts decreased with mean absorbed dose/time after 1.7 kBq 211At administration. This suggests that initial dose-rate (thus injected activity) is an important parameter in radiation-induced responses. Furthermore, the regulation profiles of groups administered 1.7 kBq were similar. Few previously proposed radiation responsive genes were identified in the present study, but, e.g. Gadd45g and Cdkn1a were among the regulated genes identified in the present study. A response involving immunological processes was identified especially at 1, 6, and 168 h after 1.7 kBq administration (0.023, 0.32, 1.8 Gy). Conclusion The present study allowed a comprehensive assessment of how variations in exposure parameters affect transcriptional regulation. The regulation profiles were dependent on both absorbed dose and time after exposure, but, initial dose-rate was the most influential parameter. Functional annotation of regulated genes revealed exposure-specific effects on biological processes. Additionally, we have identified several recurrently regulated genes after 211At exposure that may play a role in how mouse thyroid tissue responds to 211At exposure. Introduction The cellular response to stimuli can be studied on different molecular levels, including gene expression regulation. RNA microarray is a high-throughput technique that enables comparison of genome-wide transcriptional status between samples. 211At-labeled radiopharmaceuticals are potentially useful for tumor therapy. Metabolically released 211At accumulates in the thyroid gland, which is one of the main critical organs for such therapy. The aim of this study was to determine the effect of absorbed dose, dose-rate, and time after 211At exposure on transcriptional expression in mouse thyroid gland. Method BALB/c mice were i.v. injected with 1.7, 7.5 or 100 kBq 211At. Animals injected with 1.7 kBq were killed after 1, 6, or 168 h with mean absorbed doses to thyroid of 0.023, 0.32, and 1.4 Gy, respectively. Animals injected with 7.5 and 100 kBq were killed after 6 and 1 h, respectively, resulting in mean absorbed doses to thyroid of 1.4 Gy. Animals were killed through cardiac puncture under anesthesia, and thyroids were removed and snap-frozen. Total RNA was extracted from pooled thyroid tissue samples and mRNA levels were determined with the Illumina RNA microarray platform. Nexus Expression 3.0 was used to identify differentially expressed transcripts (adjusted p-value <0.01, fold change >1.5) and enriched GO terms (p-value <0.05) between irradiated groups and controls. Results In total, 1232 differentially expressed transcripts were detected after 211At administration, demonstrating a profound effect on gene regulation. The number of regulated transcripts increased with higher initial dose-rate/absorbed dose when the exposure time was 1 or 6 h. However, the number of regulated transcripts decreased with mean absorbed dose/time after 1.7 kBq 211At administration. This suggests that initial dose-rate (thus injected activity) is an important parameter in radiation-induced responses. Furthermore, the regulation profiles of groups administered 1.7 kBq were similar. Few previously proposed radiation responsive genes were identified in the present study, but, e.g. Gadd45g and Cdkn1a were among the regulated genes identified in the present study. A response involving immunological processes was identified especially at 1, 6, and 168 h after 1.7 kBq administration (0.023, 0.32, 1.8 Gy). Conclusion The present study allowed a comprehensive assessment of how variations in exposure parameters affect transcriptional regulation. The regulation profiles were dependent on both absorbed dose and time after exposure, but, initial dose-rate was the most influential parameter. Functional annotation of regulated genes revealed exposure-specific effects on biological processes. Additionally, we have identified several recurrently regulated genes after 211At exposure that may play a role in how mouse thyroid tissue responds to 211At exposure.
2015-02-20 | GSE66089 | GEO
Project description:Transcriptomic profiling of normal mouse thyroid tissue following 211At irradiation Astatine-211 (211At) is an alpha particle emitting halogen with almost optimal linear energy transfer (LET) for creating DNA double strand breaks, and is thus proposed for radionuclide therapy when bound to tumor-seeking agents. Un-bound 211At accumulates in the thyroid gland. The concept of basal radiation-induced biological effects in thyroid tissue is to a high degree unknown and is most valuable. Female BALB/c nude mice were i.v. injected with 0.064-42 kBq of 211At resulting in absorbed doses to the thyroid gland of 0.05-32 Gy. Thyroids were removed at 24 h after injection and total RNA was extracted from pooled thyroids and processed in triplicate using Illumina MouseRef-8 Whole-Genome Expression Beadchips. Nexus Expression 2.0 was used for data analysis. Thyroids exposed to 211At revealed distinctive gene expression profiles compared to non-irradiated controls. More genes were affected at low absorbed doses (0.05 and 0.5 Gy) compared to intermediate (1.4 Gy) and high absorbed doses (11 and 32 Gy) and the proportion of dose-specific genes increased with decreased absorbed dose. This result might be the manifestation of increased heterogeneous irradiation with decreasing absorbed dose, indicating a bystander effect. Also, 1.4 Gy often had an opposite regulation compared to the other absorbed doses. No inflammatory effects were seen while 0.05 and 11 Gy affected the immune system. Effects on the cellular response to outer stress and cell cycle regulation and proliferation were seen at 1.4 and 11 Gy. These results indicate that the cellular response to ionizing radiation is complex and differs with absorbed doses. Total RNA was isolated from fresh-frozen tissue samples (Normal balb/c mouse thyroids)
2013-02-13 | E-GEOD-32306 | biostudies-arrayexpress
Project description:Transcriptomic profiling of normal mouse thyroid tissue following 211At irradiation Astatine-211 (211At) is an alpha particle emitting halogen with almost optimal linear energy transfer (LET) for creating DNA double strand breaks, and is thus proposed for radionuclide therapy when bound to tumor-seeking agents. Un-bound 211At accumulates in the thyroid gland. The concept of basal radiation-induced biological effects in thyroid tissue is to a high degree unknown and is most valuable. Female BALB/c nude mice were i.v. injected with 0.064-42 kBq of 211At resulting in absorbed doses to the thyroid gland of 0.05-32 Gy. Thyroids were removed at 24 h after injection and total RNA was extracted from pooled thyroids and processed in triplicate using Illumina MouseRef-8 Whole-Genome Expression Beadchips. Nexus Expression 2.0 was used for data analysis. Thyroids exposed to 211At revealed distinctive gene expression profiles compared to non-irradiated controls. More genes were affected at low absorbed doses (0.05 and 0.5 Gy) compared to intermediate (1.4 Gy) and high absorbed doses (11 and 32 Gy) and the proportion of dose-specific genes increased with decreased absorbed dose. This result might be the manifestation of increased heterogeneous irradiation with decreasing absorbed dose, indicating a bystander effect. Also, 1.4 Gy often had an opposite regulation compared to the other absorbed doses. No inflammatory effects were seen while 0.05 and 11 Gy affected the immune system. Effects on the cellular response to outer stress and cell cycle regulation and proliferation were seen at 1.4 and 11 Gy. These results indicate that the cellular response to ionizing radiation is complex and differs with absorbed doses.
2013-02-13 | GSE32306 | GEO
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. 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.
2016-06-30 | E-GEOD-66623 | biostudies-arrayexpress
Project description:Transcriptional response in normal tissues in mice after 211At administration - dependency of absorbed dose, dose-rate and time
| PRJNA244873 | ENA
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.
2016-06-30 | GSE66623 | GEO
Project description:RNA microarray analysis of low-dose and dose rate responses versus time after i.v. administration of 211At. Female BALB/c nude mice were intravenously injected with 1.7 kBq 211At and killed after 1 h, 6 h, or 7 d, or injected with 105 or 7.5 kBq and killed after 1 h and 6 h, respectively. Controls were mock-treated. Kidneys, liver, lungs, and spleen were excised, flash-frozen, and stored at -80°C. Total RNA was extracted and subjected to expression analysis using RNA microarray technology. Enriched biological processes were categorized after cellular function based on Gene Ontology terms. Total RNA was isolated from fresh-frozen tissue samples. Three mice per group were used for 1.7 kBq 211At injections and controls; two mice per group for 105 and 7.5 kBq injections.
2015-05-01 | E-GEOD-56894 | biostudies-arrayexpress
Project description:RNA microarray analysis of low-dose and dose rate responses versus time after i.v. administration of 211At. Female BALB/c nude mice were intravenously injected with 1.7 kBq 211At and killed after 1 h, 6 h, or 7 d, or injected with 105 or 7.5 kBq and killed after 1 h and 6 h, respectively. Controls were mock-treated. Kidneys, liver, lungs, and spleen were excised, flash-frozen, and stored at -80°C. Total RNA was extracted and subjected to expression analysis using RNA microarray technology. Enriched biological processes were categorized after cellular function based on Gene Ontology terms.
2015-05-01 | GSE56894 | GEO
Project description:Transcriptomic profiling of normal mouse thyroid tissue following 131At irradiation In the present investigation, microarray analysis was used to monitor transcriptional activity in thyroids in mice 24 h after 131I exposure. The aims of this study were to 1) assess the transcriptional patterns associated with 131I exposure in normal mouse thyroid tissue and 2) identify novel biomarkers for 131I exposure. Methods: Adult BALB/c nude mice were i.v. injected with 13, 130 or 260 kBq of 131I and killed 24h after injection. The corresponding absorbed doses delivered to the thyroid gland were 0.85, 8.5, or 17 Gy. Mock-treated mice were used as controls. Total RNA was extracted from thyroids and processed using MouseRef-8 Whole-Genome Expression BeadChips (Illumina). Nexus Expression 2.0 software were used for analysis. Results: In total, 497, 546, and 90 transcripts were regulated in the thyroid after 0.85, 8.5, and 17 Gy, respectively. These were involved in several biological functions, e.g. oxygen access, inflammation and immune response, and apoptosis/anti-apoptosis. Approximately 50% of the involved transcripts at each absorbed dose level were dose-specific and 18 transcripts were commonly detected at all absorbed dose levels. The Agpat9, Plau, Prf1, and S100a8 gene expression displayed a monotone decrease in regulation with absorbed dose, and may function as dose-related biomarkers for 131I exposure. Conclusion: Distinct and substantial differences in gene expression and affected biological functions were detected at the different absorbed dose levels. The transcriptional profiles were specific for the different absorbed dose levels. We propose that the Agpat9, Plau, Prf1, and S100a8 genes are novel potential absorbed dose-related biomarkers for 131I exposure. Total RNA was isolated from fresh-frozen tissue samples (Normal Balb/c mouse thyroids)
2015-01-31 | E-GEOD-54594 | biostudies-arrayexpress