In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects bone tissue in rhesus monkeys
In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects bone tissue in rhesus monkeys
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DOI：
10.1016/j.tox.2008.09.005
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发表时间：
2008-11-20
期刊：
影响因子：
4.5
通讯作者：
Lind, P. Monica
中科院分区：
文献类型：
--
作者：
Hermsen, Sanne A. B.;Larsson, Sune;Lind, P. Monica
骨组织是二恶英和二恶英类化合物的靶组织之一。因此，本研究旨在探讨宫内和哺乳期对2，3，7，8-四氯二苯并-对二恶英(TCDD)的影响。在现有的最接近人类的实验模型恒河猴中，TCDD从妊娠第20天开始，然后每隔30天注射一次，直到分娩后90只黏土。在平均年龄7岁时，处死后代，解剖股骨。对雌性子代股骨干骺端的外周定量计算机断层扫描(PQCT)分析结果显示，与对照组相比，低剂量治疗组的骨小梁矿物质含量(BMC；+84.6%，p<；0.05，F值=5.9)显著增加。在相同的动物中，对骨干中部的分析显示总的BMC增加(+21.3%。P<；0.05，F=5.2)和皮质横截面积(CsA；+16.4%)。P<；0.01，F=7.4)。在男性中，观察到了生物力学特性的变化，表明骨骼更脆弱。男性低剂量组在失败时的位移显著高于对照组(+38.0%，p，<；0.05，F=11)。结论：宫内和哺乳期低剂量2，3.7，8-TCDD对恒河猴骨组织发育无明显影响，但不能引起高剂量2，3.7，8-TCDD对恒河猴骨组织发育的破坏，提示在人类中也可能发生类似的影响。(C)2008爱思唯尔爱尔兰有限公司。保留所有权利。
Bone tissue is one of the target tissues for dioxins and dioxin-like compounds. Therefore, the aim of this study was to investigate effects of in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), oil bone tissue in rhesus monkey, the most human-like experimental model available, Pregnant rhesus monkeys (Macaca mulatta; age 4-10 years) were exposed to TCDD with a total dose of 40.5-42.0 or 405-420 ng/kg bodyweight by repeated subcutaneous injections starting at gestational day 20 and followed by injections every 30 days until 90 clays after delivery. At a mean age of 7 years the offspring were sacrificed and the femur bone dissected. Results from peripheral Quantitative Computed Tomography (pQCT) analyses of the metaphyseal part of the femur bones in female offspring showed significant increases in trabecular bone mineral content (BMC; +84.6%, p < 0.05, F-value (F)=5.9) in the low-dose treatment group compared with the controls. In the same animals, analysis of the mid-diaphyseal part revealed increases in total BMC (+21.3%. p < 0.05, F = 5.2) and cortical cross-sectional area (CSA; +16.4%. p < 0.01, F=7.4) compared with the controls. In males, changes in biomechanical properties indicating more fragile bone were observed. Displacement at failure were significantly increased in the male low-dose group compared to the controls (+38.0%, p, < 0.05, F=11). The high dose of TCDD did not induce any significant changes in bone morphology.In conclusion, in utero and lactational low-dose, but not high-close exposure to 2,3.7,8-TCDD induced disruption of bone tissue development in rhesus monkey, a result suggesting that similar effects might occur in humans also. (C) 2008 Elsevier Ireland Ltd. All rights reserved.