Perla Venu, Perrin Nancy A, Greenlee Anne R
School of Nursing, Oregon Health and Science University, One University Boulevard, La Grande Campus, La Grande, OR 97850, USA.
Toxicol In Vitro. 2008 Mar;22(2):515-24. doi: 10.1016/j.tiv.2007.11.008. Epub 2007 Nov 17.
The objective of this in vitro study was to use a mouse embryonic stem (mES) cell model to better understand pesticide injury that may adversely affect early pregnancy and to evaluate an antioxidant intervention. Undifferentiated D3 mES cells were incubated 24h with control, reference dose (RfD), no observed effect level (NOEL), or lowest observed effect level (LOEL) of paraquat, a commonly used, toxic agricultural herbicide. Pesticide effects were evaluated at 0 and 24h using assays for cell proliferation, total reactive oxygen species (ROS), viability, and alkaline phosphatase activity. Compared to 0 h, cell proliferation increased significantly in the 24h control treatment and was stalled in all paraquat dilutions tested. ROS production and percent necrotic and apoptotic cells were significantly increased at all paraquat concentrations examined. Alkaline phosphatase activity suggested that cells remained undifferentiated during the study period. Experiments with ascorbic acid suggested that pesticide effects on cell viability and ROS production were minimized by the recommended daily allowance (RDA) of vitamin C. Data suggest pesticide-induced injury can occur very early in development and at concentrations predicted without health consequences. Mouse ES cells may provide a useful in vitro model for rapidly screening developmental toxicants and protective interventions.
这项体外研究的目的是使用小鼠胚胎干细胞（mES）模型，以更好地了解可能对早期妊娠产生不利影响的农药损伤，并评估抗氧化剂干预措施。将未分化的D3 mES细胞与常用的有毒农用除草剂百草枯的对照、参考剂量（RfD）、未观察到效应水平（NOEL）或最低观察到效应水平（LOEL）一起孵育24小时。在0小时和24小时时，使用细胞增殖、总活性氧（ROS）、活力和碱性磷酸酶活性测定法评估农药的作用。与0小时相比，24小时对照处理中的细胞增殖显著增加，而在所有测试的百草枯稀释液中细胞增殖均停滞。在所检查的所有百草枯浓度下，ROS产生以及坏死和凋亡细胞百分比均显著增加。碱性磷酸酶活性表明细胞在研究期间仍未分化。用抗坏血酸进行的实验表明，维生素C的推荐每日摄入量（RDA）可将农药对细胞活力和ROS产生的影响降至最低。数据表明，农药诱导的损伤可能在发育的很早阶段就会发生，且在预测的无健康后果的浓度下就会出现。小鼠胚胎干细胞可能为快速筛选发育毒物和保护性干预措施提供有用的体外模型。
