In utero and postnatal exposure to arsenic alters pulmonary structure and function.
In utero and postnatal exposure to arsenic alters pulmonary structure and function.
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DOI：
10.1016/j.taap.2008.11.012
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发表时间：
2009-02-15
影响因子：
3.8
通讯作者：
Chen GJ
中科院分区：
文献类型：
--
作者：
Lantz RC;Chau B;Sarihan P;Witten ML;Pivniouk VI;Chen GJ
除了癌症终点外，砷暴露还可导致非癌性慢性肺部疾病。在敏感的发育时间点暴露可导致成人疾病。使用小鼠模型，发现子宫内和产后早期暴露于砷（饮用水中100 ppb或更少）会改变28天大幼崽对乙酰甲胆碱激发的气道反应性。小鼠出生后28天从砷暴露中移除并没有逆转对乙酰甲胆碱敏感性的改变。此外，成年小鼠暴露于饮用水中类似水平的砷并没有显示出变化。因此，气道反应性的改变是不可逆的，并且对肺发育期间的暴露具有特异性。这些功能变化与蛋白质和基因表达变化以及气道周围的形态结构变化相关。砷以剂量依赖性方式增加整个肺平滑肌肌动蛋白水平。随着砷暴露的增加，气道周围平滑肌质量增加，尤其是直径小于100 μm的气道周围。平滑肌的这种增加与细胞外基质（胶原蛋白、弹性蛋白）表达的改变有关。该模型系统表明，在子宫内和出生后暴露于环境相关水平的砷可以不可逆地改变肺结构和功能的成年人。
In addition to cancer endpoints, arsenic exposures can also lead to non-cancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic (100 ppb or less in drinking water) were found to alter airway reactivity to methacholine challenge in 28 day old pups. Removal of mice from arsenic exposure 28 days after birth did not reverse the alterations in sensitivity to methacholine. In addition, adult mice exposed to similar levels of arsenic in drinking water did not show alterations. Therefore, alterations in airway reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Arsenic increased the whole lung levels of smooth muscle actin in a dose dependent manner. The level of smooth muscle mass around airways was increased with arsenic exposure, especially around airways smaller than 100 μm in diameter. This increase in smooth muscle was associated with alterations in extracellular matrix (collagen, elastin) expression. This model system demonstrates that in utero and postnatal exposure to environmentally relevant levels of arsenic can irreversibly alter pulmonary structure and function in the adults.
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影响因子：
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作者：
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影响因子：
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作者：
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