| 31. |
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| 32. |
- Langen, Britta, et al.
(författare)
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Non-targeted transcriptomic effects upon thyroid irradiation: similarity between in-field and out-of-field responses varies with tissue type
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Non-targeted effects can induce responses in tissues that have not been exposed to ionizing radiation. Despite their relevance for risk assessment, few studies have investigated these effects in vivo. In particular, these effects have not been studied in context with thyroid exposure, which can occur e.g. during irradiation of head and neck tumors. To determine the similarity between in-field and out-offield responses in normal tissue, we used a partial body irradiation setup with female mice where the thyroid region, the thorax and abdomen, or all three regions were irradiated. After 24h, transcriptional regulation in the kidney cortex, kidney medulla, liver, lungs, spleen, and thyroid was analyzed using microarray technology. Thyroid irradiation resulted in transcriptional regulation in the kidney medulla and liver that resembled regulation upon direct exposure of these tissues regarding both strength of response and associated biological function. The kidney cortex showed fewer similarities between the setups, while the lungs and spleen showed little similarity between in-field and out-of-field responses. Interestingly, effects were generally not found to be additive. Future studies are needed to identify the molecular mechanisms that mediate these systemic effects, so that they may be used as targets to minimize detrimental side effects in radiotherapy.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Langen, Britta, et al.
(författare)
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Thyroid irradiation and non-targeted effects: in-field and out-of-field responses on the transcriptomic level show tissue-specific similarity
- 2016
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Ingår i: SweRays Workshop, Stockholm, Sweden, Aug 25-26.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Radiation exposure can result in non-targeted effects that strongly influence cellular responses in non-irradiated tissues. However, radiotherapy planning does not consider out-of-field effects in current risk assessment, because knowledge of these effects is still scarce. Non-targeted effects from the thyroid are of particular concern, since it is a major regulatory gland and often subject to exposure during irradiation of e.g. head and neck, lung and breast tumors. The aim of this study was to characterize in-field and out-of-field responses on the transcriptomic level in vivo after thyroid irradiation. Methods: Anaesthetized female BALB/c nude mice were irradiated with 2 Gy from 4 MV photon beams in a partial body irradiation setup: the thyroid region, the thorax and abdomen, or all three regions combined (n=3/group). Control mice (n=5) were anaesthetized but not irradiated. Mice were killed after 24h and the kidneys, liver, lungs, spleen, and thyroid were sampled. Expression microarray analysis was performed on total RNA extracted from tissue samples. Results: Thyroid irradiation induced complex gene regulation responses in kidney medulla and liver that were highly similar to direct exposure of these tissues. In contrast, kidney cortex showed a lesser degree of similarity between setups, while lungs and spleen exhibited only marginal out-of-field responses. Interestingly, non-targeted effects and in-field responses did not appear to show simple additive behavior. Conclusions: Thyroid exposure can induce significant responses in other tissues similar to direct irradiation, but these non-targeted effects show tissue-specificity. The underlying mechanisms may yield molecular targets for minimizing systemic side-effects in radiotherapy.
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| 37. |
- Langen, Britta, et al.
(författare)
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Transcriptional response in normal mouse tissues after i.v. 211At administration - response related to absorbed dose, dose rate, and time
- 2015
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X .- 2191-219X. ; 5:1, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Background In cancer radiotherapy, knowledge of normal tissue responses and toxicity risks is essential in order to deliver the highest possible absorbed dose to the tumor while maintaining normal tissue exposure at non-critical levels. However, few studies have investigated normal tissue responses in vivo after 211At administration. In order to identify molecular biomarkers of ionizing radiation exposure, we investigated genome-wide transcriptional responses to (very) low mean absorbed doses from 211At in normal mouse tissues. Methods Female BALB/c nude mice were intravenously injected with 1.7 kBq 211At and killed after 1 h, 6 h, or 7 days or injected with 105 or 7.5 kBq and killed after 1 and 6 h, respectively. Controls were mock-treated. Total RNA was extracted from tissue samples of kidney cortex and medulla, liver, lungs, and spleen and subjected to microarray analysis. Enriched biological processes were categorized after cellular function based on Gene Ontology terms. Results Responses were tissue-specific with regard to the number of significantly regulated transcripts and associated cellular function. Dose rate effects on transcript regulation were observed with both direct and inverse trends. In several tissues, Angptl4, Per1 and Per2, and Tsc22d3 showed consistent transcript regulation at all exposure conditions. Conclusions This study demonstrated tissue-specific transcriptional responses and distinct dose rate effects after 211At administration. Transcript regulation of individual genes, as well as cellular responses inferred from enriched transcript data, may serve as biomarkers in vivo. These findings expand the knowledge base on normal tissue responses and may help to evaluate and limit side effects of radionuclide therapy. Keywords: Astatine-211; Ionizing radiation; Normal tissue response; Radionuclide therapy; Biomarke
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| 38. |
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| 39. |
- Larsson, Malin, et al.
(författare)
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Age-related long-term response in rat thyroid tissue and plasma after internal low dose exposure to I-131
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- I-131 is used clinically for therapy, and may be released during nuclear accidents. After the Chernobyl accident papillary thyroid carcinoma incidence increased in children, but not adults. The aims of this study were to compare I-131 irradiation-dependent differences in RNA and protein expression in the thyroid and plasma of young and adult rats, and identify potential age-dependent biomarkers for I-131 exposure. Twelve young (5 weeks) and twelve adult Sprague Dawley rats (17 weeks) were i.v. injected with 50 kBq I-131 (absorbed dose to thyroid = 0.1 Gy), and sixteen unexposed age-matched rats were used as controls. The rats were killed 3-9 months after administration. Microarray analysis was performed using RNA from thyroid samples, while LC-MS/MS analysis was performed on proteins extracted from thyroid tissue and plasma. Canonical pathways, biological functions and upstream regulators were analysed for the identified transcripts and proteins. Distinct age-dependent differences in gene and protein expression were observed. Novel biomarkers for thyroid I-131 exposure were identified: (PTH), age-dependent dose response (CA1, FTL1, PVALB (youngsters) and HSPB6 (adults)), thyroid function (Vegfb (adults)). Further validation using clinical samples are needed to explore the role of the identified biomarkers.
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