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- 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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- 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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- 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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- Saadati, Sofia, 1992, et al.
(författare)
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Early indications on UVC-related carcinogenesis: premutagenic DNA damage in mice following 222-nm light exposure
- 2016
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Ingår i: 4th Swedish Cancer Research Meeting, Gothenburg, Sweden, November 7-8, 2016.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Surgical site infections, caused by air borne bacteria and viruses, can have lethal consequences. The use of conventional germicidal UV lamps, emitting primarily 254-nm light, at the surgical site has been prevented by being cancerogenic. Far-UVC light (200-222 nm) has been shown to be equieffective without being as damaging to human cells in vitro. In mammalian skin, it is DNA-damage in the basal cells that contributes to the major risk of cancer induction. The aim was to test the hypothesis that 222-nm light is less premutagenic than 254-nm light in vivo. SKH1 mice were exposed to different doses of 222-nm light and compared with positive (254-nm light) and negative (sham irradiated) controls. The mice were killed after 48h and dorsal skin samples were excised. UV specific DNA-damage cyclobutane pyrimidine dimer (CPD) was assessed by immunohistochemical analysis and a damage depth profile was determined. Loss of light intensity was also determined using phantoms with different protein concentrations, simulating various depths in skin. While the amount of CPD was significantly lower following 222-nm light in comparison with 254-nm light at all epidermal depths, no difference was seen in comparison with negative controls. Absorption of 222-nm light was much higher than 254-nm light. Results show that 222-nm light, for the investigated doses, does not appear to be premutagenic. These promising results indicate the potentials of far-UVC lamps as a disinfecting tool without patient and staff being subject to hazardous exposure.
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