Department of Biology, 163 Packard Avenue, Dana Hall, Tufts University, Medford, MA 02155, USA.
J Appl Toxicol. 2010 Aug;30(6):582-9. doi: 10.1002/jat.1529.
Exposure to the herbicide atrazine disrupts many developmental processes in non-target animals. Atrazine exposure during organ morphogenesis in amphibians results in dramatic malformations; the mechanism by which this happens has not been described. We have taken a candidate gene approach to explore two possible mechanisms by which acute atrazine exposure causes extensive malformations in several tissues in Xenopus laevis tadpoles. Using a static renewal system, we exposed tadpoles to atrazine for 6-48 h during organ morphogenesis (Nieuwkoop and Faber stage 42). We observed degradation of cranial cartilage and differentiated muscle in the head, gut and somites of exposed tadpoles. Additionally, transcript levels of matrix metalloproteinases (MMPs), specifically both MMP9TH and MMP18, increased in atrazine-exposed tadpoles in a dose-response test, and MMP18 increased as early as 6 h after exposure began. Gelatinase MMP activity was also altered by atrazine exposure, indicating that atrazine disrupts gene function at the level of transcription and protein activity. Furthermore, transcript levels of the enzyme Xcyp26, an enzyme in the retinoic acid signaling pathway, significantly decreased in the intestines of tadpoles exposed to 10 or 35 mg l(-1) atrazine for 48 h. Our results suggest two mechanisms by which atrazine can disrupt tissue morphogenesis: through misregulation of MMPs that are critical in extracellular matrix remodeling throughout development and the disruption of retinoic acid signaling. This study begins to describe conserved vertebrate developmental processes that are disrupted by atrazine exposure.
暴露于莠去津这种除草剂会扰乱非靶标动物的许多发育过程。在两栖动物器官形态发生过程中暴露于莠去津会导致明显的畸形；其发生的机制尚未描述。我们采用候选基因方法探索了莠去津急性暴露导致非洲爪蟾蝌蚪几个组织广泛畸形的两种可能机制。使用静态更新系统，我们在器官形态发生过程中（Nieuwkoop 和 Faber 阶段 42）将蝌蚪暴露于莠去津 6-48 小时。我们观察到暴露的蝌蚪的头部、肠道和体节中的颅软骨和分化的肌肉降解。此外，在莠去津暴露的蝌蚪的剂量反应试验中，基质金属蛋白酶（MMPs）的转录水平，特别是 MMP9TH 和 MMP18，增加，并且 MMP18 在暴露开始后 6 小时即可增加。明胶酶 MMP 活性也被莠去津暴露改变，表明莠去津在转录和蛋白质活性水平上破坏基因功能。此外，暴露于 10 或 35 mg l(-1)莠去津 48 小时的蝌蚪的肠道中，视黄酸信号通路中的酶 Xcyp26 的转录水平显著降低。我们的结果表明莠去津可以破坏组织形态发生的两种机制：通过对在整个发育过程中对细胞外基质重塑至关重要的 MMPs 的失调，以及对视黄酸信号的破坏。这项研究开始描述被莠去津暴露破坏的保守脊椎动物发育过程。
