Transcriptional response in normal tissues in mice after 211At administration - dependency of absorbed dose, dose-rate and time
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Britta Langen
PROVIDER: E-GEOD-56894 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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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 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 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:Circadian rhythm study on transcriptional responses to i.v. administered 90 kBq iodine-131 after 24h in mouse kidney cortex and medulla, liver, lungs, spleen, and thyroid. Female BALB/c nude mice (n=4/group) were i.v. injected with 90 kBq 131I at three different times of day, i.e. at 9.00 am, at 12.00 pm, or at 3.00 pm, and killed under anesthesia after 24h following treatment for excision of organs. For each time of day, a control group (n=3-4/group) was i.v. injected with physiol. saline. The kidneys, liver, lungs, spleen, and thyroid were excised, flash-frozen, and stored at -80°C until extraction of total RNA. Total RNA was extracted from homogenized tissue samples and subjected to expression analysis using RNA microarray technology. The study consisted of 6 groups in total, i.e. 3 groups (n=4/group) that were i.v. injected with 90 kBq 131I (at 9.00 am, 12.00 pm, or 3.00 pm) and 3 sham-treated control groups (n=3-4/group) that were i.v. injected with physiol. saline (at 9.00 am, 12.00 pm, or 3.00 pm); please note that the number of control animals varied between 3-4 animals per group, i.e. n=4 treated at 9.00 am, n=3 treated at 12.00 pm, and n=3 treated at 3.00 pm. Six tissues were analyzed per animal, i.e. kidney cortex, kidney medulla, liver, lungs, spleen, and thyroid.
2016-03-31 | E-GEOD-66303 | biostudies-arrayexpress
Project description:Circadian rhythm study on transcriptional responses to i.v. administered 90 kBq iodine-131 after 24h in mouse kidney cortex and medulla, liver, lungs, spleen, and thyroid. Female BALB/c nude mice (n=4/group) were i.v. injected with 90 kBq 131I at three different times of day, i.e. at 9.00 am, at 12.00 pm, or at 3.00 pm, and killed under anesthesia after 24h following treatment for excision of organs. For each time of day, a control group (n=3-4/group) was i.v. injected with physiol. saline. The kidneys, liver, lungs, spleen, and thyroid were excised, flash-frozen, and stored at -80°C until extraction of total RNA. Total RNA was extracted from homogenized tissue samples and subjected to expression analysis using RNA microarray technology.
2016-03-31 | GSE66303 | 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.
2013-02-13 | GSE32306 | 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:Short day (8hrs of light/day) housed juvenile, male F344 rats were injected with 10^-5 M all-trans RA or vehicle (saline) into the third ventricle of the hypothalamus. 24 hours after RA injections rats were killed by decapitation after isoflurane inhalation at ZT3 and brains were dissected and frozen on dry ice. Hypothalamic arcuate nucleus tissue blocks were cut for RNA exaction. 4 rats per group were used giving 8 rats in total.
2015-12-01 | GSE65300 | GEO
Project description:Background. Radioiodide 131I is commonly used to treat thyroid cancer and hyperthyroidism, and 131I releases during nuclear accidents have resulted in increased incidence of thyroid cancer in children. To develop a better understanding of underlying cellular mechanisms behind 131I exposure and identify potential biomarkers, the aim of this work was to study the long-term dose-related effects of 131I exposure in thyroid tissue and plasma in young rats. Materials and methods. Male Sprague Dawley rats (5-week-old) were i.v. injected with 0.5, 5.0, 50 or 500 kBq 131I (Dthyroid ca 1–1000 mGy), and killed after nine months at which time the thyroid and blood samples were collected. Gene expression microarray analysis (thyroid samples) and LC-MS/MS analysis (thyroid and plasma samples) were performed to assess differential gene and protein expression patterns in treated and corresponding untreated control samples. Bioinformatics analyses were performed using the DAVID functional annotation tool and Ingenuity Pathway Analysis (IPA). Results. Nine 131I exposure-related biomarkers (Afp and RT1-Bb,ARF3, DLD, IKBKB, NONO, RAB6A, RPN2, and SLC25A5) were identified in thyroid tissue. Four dose-related biomarker candidates (APRT, LDHA) and (TGM3 and DSG4) were identified in thyroid and plasma, respectively. Candidate biomarkers for thyroid function were the upstream regulator PPARG and the proteins ACADL and SORBS2 (all activities), TPO and TG (low activities)). 131I exposure was shown to have a profound effect on metabolism, the immune system, apoptosis and cell death. Furthermore, several signalling pathways essential for normal cellular function (actin cytoskeleton signalling, HGF signalling, NRF2-mediated oxidative stress, integrin signalling, calcium signalling) were also significantly regulated. Conclusion. Exposure-related and dose-related effects on gene and protein expression were observed, thereby identifying several candidate genes that could be used as potential biomarkers for exposure, absorbed dose and thyroid function.
2020-12-07 | PXD017715 | Pride
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.
2015-01-31 | GSE54594 | GEO