Spirhanzlova Petra, De Groef Bert, Nicholson Freda E, Grommen Sylvia V H, Marras Giulia, Sébillot Anthony, Demeneix Barbara A, Pallud-Mothré Sophie, Lemkine Gregory F, Tindall Andrew J, Du Pasquier David
Laboratoire WatchFrog S.A., 1 Rue Pierre Fontaine, 91000 Évry, France; UMR CNRS 5166, Evolution des Régulations Endocriniennes, Department of Regulation, Development and Molecular Diversity, Muséum National d'Histoire Naturelle, Paris, France.
Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, Victoria 3086, Australia.
Comp Biochem Physiol C Toxicol Pharmacol. 2017 Oct;200:52-58. doi: 10.1016/j.cbpc.2017.06.006. Epub 2017 Jun 17.
Several short-term whole-organism bioassays based on transgenic aquatic models are now under validation by the OECD (Organization for Economic Co-operation and Development) to become standardized test guidelines for the evaluation of the endocrine activity of substances. Evaluation of the endocrine disrupting capacity of pesticides will be a domain of applicability of these future reference tests. The herbicide linuron and the insecticide fenoxycarb are two chemicals commonly used in agricultural practices. While numerous studies indicate that linuron is likely to be an endocrine disruptor, there is little information available on the effect of fenoxycarb on vertebrate endocrine systems. Using whole-organism bioassays based on transgenic Xenopus laevis tadpoles and medaka fry we assessed the potential of fenoxycarb and linuron to disrupt thyroid, androgen and estrogen signaling. In addition we used in silico approach to simulate the affinity of these two pesticides to human hormone receptors. Linuron elicited thyroid hormone-like activity in tadpoles at all concentrations tested and, showed an anti-estrogenic activity in medaka at concentrations 2.5mg/L and higher. Our experiments suggest that, in addition to its previously established anti-androgenic action, linuron exhibits thyroid hormone-like responses, as well as acting at the estrogen receptor level to inhibit estrogen signaling. Fenoxycarb on the other hand, did not cause any changes in thyroid, androgen or estrogen signaling at the concentrations tested.
经济合作与发展组织（OECD）目前正在验证几种基于转基因水生模型的短期全生物体生物测定法，使其成为评估物质内分泌活性的标准化测试指南。评估农药的内分泌干扰能力将是这些未来参考测试的一个适用领域。除草剂利谷隆和杀虫剂苯氧威是农业实践中常用的两种化学品。虽然大量研究表明利谷隆可能是一种内分泌干扰物，但关于苯氧威对脊椎动物内分泌系统影响的信息却很少。我们利用基于转基因非洲爪蟾蝌蚪和青鳉幼鱼的全生物体生物测定法，评估了苯氧威和利谷隆干扰甲状腺、雄激素和雌激素信号传导的潜力。此外，我们还采用计算机模拟方法来模拟这两种农药对人类激素受体的亲和力。在所测试的所有浓度下，利谷隆在蝌蚪中引发了甲状腺激素样活性，并且在浓度为2.5mg/L及更高时，在青鳉中表现出抗雌激素活性。我们的实验表明，除了其先前确定的抗雄激素作用外，利谷隆还表现出甲状腺激素样反应，并作用于雌激素受体水平以抑制雌激素信号传导。另一方面，在所测试的浓度下，苯氧威并未引起甲状腺、雄激素或雌激素信号传导的任何变化。
