Neural Tube Defects in Mice Exposed to Tap Water
Neural Tube Defects in Mice Exposed to Tap Water
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DOI：
10.1002/tox.20600
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发表时间：
2011-11-01
影响因子：
4.5
通讯作者：
Hrubec, Terry C.
中科院分区：
文献类型：
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作者：
Mallela, Murali K.;Werre, Stephen R.;Hrubec, Terry C.
2006年5月，我们突然开始在未经处理的对照小鼠胚胎中观察到神经管缺陷（NTD）。我们假设小鼠在不知情的情况下暴露于致畸剂，并调查了原因。我们的研究结果表明，NTDs不是由垫料，饲料，品系，或小鼠的来源。此外，小鼠对病原体的常规和全面筛查呈阴性。为了进一步测试NTD是否由我们机构的感染或遗传原因引起，我们从位于四个不同州的商业供应商处获得了三种定时妊娠小鼠。所有品系和来源的小鼠均携带NTD到达我们的实验室，这意味着市售小鼠在购买前可能暴露于致畸剂。我们的调查最终得出结论，接触自来水是导致NTD的原因。NTD的发生率最高的购买小鼠提供自来水和最低的购买小鼠提供蒸馏去离子水（DDI）。给两代小鼠提供DDI水（F2-DDI）消除了NTD。当F2-DDI小鼠在繁殖前从三个不同的城市地区提供自来水时，它们的后代再次出现NTD。接触自来水时间的增加显着增加了NTD的发病率。这些结果表明，城市自来水中的污染物可能导致小鼠NTD。未知的致畸剂似乎有广泛的地理分布，但尚未确定。目前正在进行水分析，以确定可能导致畸形的候选污染物。(C)2010 Wiley Periodicals，Inc.环境毒理学26：633-640，2011年。
In May of 2006 we suddenly began to observe neural tube defects (NTDs) in embryos of untreated control mice. We hypothesized the mice were being exposed unknowingly to a teratogenic agent and investigated the cause. Our results suggested that NTDs were not resulting from bedding material, feed, strain, or source of the mice. Additionally, mice were negative for routine and comprehensive screens of pathogens. To further test whether the NTDs resulted from infectious or genetic cause localized to our facility, we obtained three strains of timed pregnant mice from commercial suppliers located in four different states. All strains and sources of mice arrived in our laboratory with NTDs, implying that commercially available mice were possibly exposed to a teratogen prior to purchase. Our investigation eventually concluded that exposure to tap water was causing the NTDs. The incidence of NTDs was greatest in purchased mice provided tap water and lowest in purchased mice provided distilled deionized water (DDI). Providing mice DDI water for two generations (F2-DDI) eliminated the NTDs. When F2-DDI mice were provided tap water from three different urban areas prior to breeding, their offspring again developed NTDs. Increased length of exposure to tap water significantly increased the incidence of NTDs. These results indicate that a contaminant in municipal tap water is likely causing NTDs in mice. The unknown teratogen appears to have a wide geographic distribution but has not yet been identified. Water analysis is currently underway to identify candidate contaminants that might be responsible for the malformations. (C) 2010 Wiley Periodicals, Inc. Environ Toxicol 26: 633-640, 2011.