Tissue-Specific and Dose-Related Accumulation of Arsenic in Mouse Offspring Following Maternal Consumption of Arsenic-Contaminated Water
Tissue-Specific and Dose-Related Accumulation of Arsenic in Mouse Offspring Following Maternal Consumption of Arsenic-Contaminated Water
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DOI：
10.1111/j.1742-7843.2010.00660.x
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发表时间：
2011-05-01
影响因子：
3.1
通讯作者：
Wise, John P., Sr.
中科院分区：
文献类型：
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作者：
Markowski, Vincent P.;Currie, Douglas;Wise, John P., Sr.
砷的发育毒性不如铅或汞等其他金属。以前的许多动物研究都采用了急性接触模式，但没有模拟慢性、低水平的人类接触。以下研究向怀孕的C57 BL 6/J小鼠给予含10、20、40、80或100 ppm亚砷酸钠的饮用水。在出生后第1天和第21天（PND）采集雄性和雌性后代的脂肪、血液、脑、胃、肾和肝组织中的母乳，以进行组织、性别和时间之间的处置比较。100 ppm剂量具有胎儿毒性。在暴露于80 ppm的窝中出生的雌性幼仔明显较少，而在暴露于20 ppm的窝中出生的雄性幼仔明显较多。在PND 1后代中，脑和肾脏中的总砷水平在组织之间存在差异。PND 1的水平高于PND 21，并且几乎没有性别差异。PND 1组织中砷的剂量-反应关系呈曲线型，而PND 21肝、肾组织中对照组的砷含量显著高于染毒组。组织和年龄特异性的处置表明，常见的生物标志物，如血液和尿砷是不准确的预测水平在敏感器官，如大脑。
The developmental toxicity of arsenic is not as well characterized as other metals such as lead or mercury. Many previous animal studies have used an acute exposure paradigm, which does not model chronic, low-level human exposure. The following study administered 10, 20, 40, 80 or 100 ppm sodium arsenite in drinking water to pregnant C57BL6/J mice. Adipose, blood, brain, breastmilk in stomach, kidney and liver tissues were collected from male and female offspring on postnatal day (PND) 1 and 21 to allow for disposition comparisons between tissues, sexes and across time. The 100 ppm dose was foetotoxic. Significantly fewer female pups were born in litters exposed to 80 ppm, while significantly more male pups were born in litters exposed to 20 ppm. Total arsenic levels differed between tissues with the highest levels in the brain and kidney in PND1 offspring. Levels were higher on PND1 than PND21, and there were few sex differences. The dose-response relationships in PND1 tissues were curvilinear, but in PND21 liver and kidney tissues, arsenic levels in control animals were significantly higher than levels in exposed animals. The tissue and age-specific disposition suggests that common biomarkers such as blood and urinary arsenic are not accurate predictors of levels in sensitive organs such as the brain.