| 31. |
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| 32. |
- 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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| 33. |
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| 34. |
- Larsson, Maria, 1972, et al.
(författare)
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Kidney toxicity in mice treated with 177Lu-octreotate
- 2012
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Ingår i: 25th Annual Congress on European Association of Nuclear Medicine, Milano, Italy, October 27-31, 2012 . (European Journal of Nuclear Medicine and Molecular Imaging). - 1619-7070.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 35. |
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| 36. |
- Larsson, Malin, et al.
(författare)
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Long-term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I exposure.
- 2020
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 15:12
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Tidskriftsartikel (refereegranskat)abstract
- Radioiodide (131I) is commonly used to treat thyroid cancer and hyperthyroidis.131I released during nuclear accidents, have resulted in increased incidence of thyroid cancer in children. Therefore, a better understanding of underlying cellular mechanisms behind 131I exposure is of great clinical and radiation protection interest. 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 and identify potential biomarkers.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 profiles in treated and corresponding untreated control samples. Bioinformatics analyses were performed using the DAVID functional annotation tool and Ingenuity Pathway Analysis (IPA). The gene expression microarray data and LC-MS/MS data were validated using qRT-PCR and ELISA, respectively.Nine 131I exposure-related candidate biomarkers (transcripts: Afp and RT1-Bb, and proteins: ARF3, DLD, IKBKB, NONO, RAB6A, RPN2, and SLC25A5) were identified in thyroid tissue. Two dose-related protein candidate biomarkers were identified in thyroid (APRT and LDHA) and two in plasma (DSG4 and TGM3). Candidate biomarkers for thyroid function included the ACADL and SORBS2 (all activities), TPO and TG proteins (low activities). 131I exposure was shown to have a profound effect on metabolism, 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.Exposure-related and dose-related effects on gene and protein expression generated few expression patterns useful as biomarkers for thyroid function and cancer.
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| 37. |
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| 38. |
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| 39. |
- Larsson, Malin, et al.
(författare)
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Transcriptome and proteome analysis for potential biomarker discovery of long-term effects in rat thyroid and blood tissue after I-131 exposure
- 2016
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Ingår i: SweRays Workshop, Stockholm, Sweden, Aug 25-26.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- After the Chernobyl accident, an increased incidence of thyroid cancer was seen in children due to exposure from 131I fallout. The aim of this study was to identify biomarkers for long-term effects in vivo related to carcinogenesis and thyroid function. Young male Sprague Dawley rats (5w) were i.v. injected with 0, 0.50, 5, 50, or 500 kBq 131I (Dthyroid = 0 ̶ 10 Gy), and adult rats (17w) were i.v. injected with 0 and 50 kBq 131I (Dthyroid = 0 ̶ 1 Gy). Thyroid and blood samples were collected after termination at three, six, or nine months after injection. Gene expression analysis was performed on total RNA extracted from thyroids using the Agilent microarray platform. Differentially regulated transcripts were identified using Nexus Expression 3.0. LC-MS/MS was performed to analyze protein expression in thyroid and blood. Gene and protein expression in response to 131I differed with time and age-at-exposure. Interesting dosedependent transcripts were identified, for instance, after nine months (young rats). The number of proteins with altered level was 3111 in thyroid and 1213 in blood. For example, the CLIP2 (biomarker candidate for thyroid cancer) level in blood differed between young and old rats. At six months the level was increased for young and decreased for old rats, but opposite pattern was seen after nine months. For the threemonth- groups, the level was increased for young and old rats. In conclusion, potential biomarker candidates for 131I exposure were found in rat thyroid and blood and will be further studied.
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| 40. |
- Parris, Toshima Z, 1978, et al.
(författare)
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Proteomic analysis of normal mouse thyroids after 131I administration
- 2015
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Ingår i: 15th International Congress of Radiation Research, Kyoto, Japan, May 25-29.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Iodine is essential for the normal function of the thyroid gland, which in turn is susceptible to cellular damage after treatment with the β-emitter radioiodine (131I). Individuals exposed to 131I at a young age via contaminated food or nuclear crises such as the Chernobyl nuclear accident are at greater risk of developing e.g. thyroid cancer and other thyroid disorders later on in life. These factors may therefore have clinical implications for patients receiving 131I-based radionuclide therapy. The aim of this study was to identify potential biomarkers in normal thyroid tissue that are induced by 131I administration. Non-tumor-bearing female Balb/c nude mice were i.v. injected with 490 kBq 131I or physiological saline and killed 24 h after injection. The mean absorbed dose to the thyroid was calculated to 32 Gy. Protein lysates were extracted from surgically excised thyroids and analyzed using liquid chromatography tandem-mass spectrometry (LC-MS/MS), followed by database-dependent protein identification and relative quantification. The LC-MS/MS analysis identified 17 differentially expressed proteins (p<0.05), of which 13 showed down-regulation in the 131I-treated group compared to the controls. There was an enrichment of proteins associated with hypoxia/ischemia, oxygen transport/erythrocyte development, regulation of cell cycle, and metabolism. Interestingly, Hypoxia up-regulated protein 1 (HYOU1), known to be up-regulated during hypoxic conditions, was up-regulated in treated samples. In addition, five proteins associated with oxygen transport/erythrocyte development were identified, all of which were down-regulated, i.e. Bisphosphoglycerate mutase (PMGE), Ankyrin-1 (ANK1), and Hemoglobin subunits beta-1 (HBB1), beta-2 (HBB2), alpha (HBA). Taken together, these findings suggest the presence of hypoxic conditions and reduced oxygen transport in normal mouse thyroids 24 h after 131I administration. However, further studies are needed to determine whether these effects are time- and/or dose-dependent.
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