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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 04477naa a2200469 4500 | |
| 001 | oai:DiVA.org:uu-126135 | |
| 003 | SwePub | |
| 008 | 100603s2010 | |||||||||||000 ||eng| | |
| 009 | oai:prod.swepub.kib.ki.se:120947387 | |
| 024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1261352 URI |
| 024 | 7 | a https://doi.org/10.1016/j.tox.2010.04.0062 DOI |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1209473872 URI |
| 040 | a (SwePub)uud (SwePub)ki | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Herlin, Mariau Karolinska Institutet4 aut |
| 245 | 1 0 | a Quantitative characterization of changes in bone geometry, mineral density and biomechanical properties in two rat strains with different Ah-receptor structures after long-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin |
| 264 | 1 | b Elsevier BV,c 2010 |
| 338 | a print2 rdacarrier | |
| 520 | a BACKGROUND: Both industrial chemicals and environmental pollutants can interfere with bone modeling and remodeling. Recently, detailed toxicological bone studies have been performed following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which exerts most of its toxic effects through the aryl hydrocarbon receptor (AhR). OBJECTIVES: The aims of the present study were to quantitatively evaluate changes in bone geometry, mineral density and biomechanical properties following long-term exposure to TCDD, and to further investigate the role of AhR in TCDD-induced bone alterations. To this end, tissue material used in the study was derived from TCDD-exposed Long-Evans (L-E) and Han/Wistar (H/W) rats, which differ markedly in sensitivity to TCDD-induced toxicity due to a strain difference in AhR structure. METHODS: Ten weeks old female L-E and H/W rats were administered TCDD s.c. once per week for 20 weeks, at doses corresponding to calculated daily doses of 0, 1, 10, 100 and 1000ngTCDD/kgbw (H/W only). Femur, tibia and vertebra from the L-E and H/W rats were analyzed by peripheral quantitative computed tomography (pQCT) and biomechanical testing at multiple sites. Dose-response modeling was performed to establish benchmark doses for the analyzed bone parameters, and to quantify strain sensitivity differences for those parameters, which were affected by TCDD exposure in both rat strains. RESULTS: Bone geometry and bone biomechanical parameters were affected by TCDD exposure, while bone mineral density parameters were less affected. The trabecular area at proximal tibia and the endocortical circumference at tibial diaphysis were the parameters that showed the highest maximal responses. Significant strain differences in response to TCDD treatment were observed, with the L-E rat being the most sensitive strain. For the parameters that were affected in both strains, the differences in sensitivity were quantified, showing the most pronounced (about 49-fold) strain difference for cross-sectional area of proximal tibia. CONCLUSION: The study provides novel information about TCDD-induced bone alterations at doses, which are of relevance from a health risk assessment point of view. In addition, the obtained results provide further support for a distinct role of the AhR in TCDD-induced bone alterations, and suggest that the benchmark dose modeling approach is appropriate for quantitative evaluation of bone toxicity parameters. | |
| 653 | a MEDICINE | |
| 653 | a MEDICIN | |
| 653 | a Orthopaedics | |
| 653 | a Ortopedi | |
| 700 | 1 | a Kalantari, Fereshtehu Karolinska Institutet4 aut |
| 700 | 1 | a Stern, Natalia4 aut |
| 700 | 1 | a Sand, Salomon4 aut |
| 700 | 1 | a Larsson, Suneu Uppsala universitet,Ortopedi4 aut0 (Swepub:uu)sunelars |
| 700 | 1 | a Viluksela, Matti4 aut |
| 700 | 1 | a Tuomisto, Jouni T.4 aut |
| 700 | 1 | a Tuomisto, Jouko4 aut |
| 700 | 1 | a Tuukkanen, Juha4 aut |
| 700 | 1 | a Jämsä, Timo4 aut |
| 700 | 1 | a Lind, Monicau Uppsala universitet,Arbets- och miljömedicin,Eva Vingård4 aut0 (Swepub:uu)monilind |
| 700 | 1 | a Håkansson, Helenu Karolinska Institutet4 aut |
| 710 | 2 | a Karolinska Institutetb Ortopedi4 org |
| 773 | 0 | t Toxicologyd : Elsevier BVg 273:1-3, s. 1-11q 273:1-3<1-11x 0300-483Xx 1879-3185 |
| 856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-126135 |
| 856 | 4 8 | u https://doi.org/10.1016/j.tox.2010.04.006 |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:120947387 |
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