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五氯苯甲醚和五氯苯酚在斑马鱼模型中的相对发育毒性。

Relative developmental toxicities of pentachloroanisole and pentachlorophenol in a zebrafish model (Danio rerio).

机构信息

Center for Advanced Research in Environmental Genomics, University of Ottawa, 30 Marie Curie, Ottawa, ON, Canada K1N 6N5.

Center for Advanced Research in Environmental Genomics, University of Ottawa, 30 Marie Curie, Ottawa, ON, Canada K1N 6N5.

出版信息

Ecotoxicol Environ Saf. 2015 Feb;112:7-14. doi: 10.1016/j.ecoenv.2014.10.004. Epub 2014 Nov 4.

Abstract

Pentachloroanisole (PCA) and pentachlorophenol (PCP) are chlorinated aromatic compounds that have been found in the environment and in human populations. The objective of this study is to characterize the effects of PCA in comparison to those of PCP on development at environmental relevant levels using a fish model. Zebrafish embryos were exposed to 0.1, 1, 10, 100, 500, 1000 μg/L PCA and PCP respectively for 96 h. Malformation observation, LC50 testing for survival rate at 96 hours post fertilization (hpf) and EC50 testing for hatching rate at 72 hpf indicated that the developmental toxicity of PCP was about 15 times higher than that of PCA. PCP exposure at 10 μg/L resulted in elevated 3, 3', 5-triiodothyronine (T3) levels and decreased thyroxine (T4) levels, whereas PCA had no effects on T3 or T4 levels. PCP and PCA exposure at 1 and 10 μg/L showed possible hyperthyroid effects similar to that of T3, due to increased relative mRNA expression of synapsin I (SYN), iodothyronine deiodinase type III (Dio3), thyroid hormone receptor alpha a (THRαa) and thyroid hormone receptor beta (THRβ), and decreased expression of iodothyronine deiodinase type II (Dio2). The results indicate that both PCA and PCP exposure can cause morphological deformities, possibly affect the timing and coordination of development in the central nervous system, and alter thyroid hormone levels by disrupting thyroid hormone regulating pathways. However, the developmental toxicity of PCA is at least ten times lower than that of PCP. Our results on the relative developmental toxicities of PCA and PCP and the possible underlying mechanisms will be useful to support interpretation of envrionmental concentrations and body burden levels observed in human populations.

摘要

五氯苯甲醚(PCA)和五氯苯酚(PCP)是两种在环境中和人类群体中均有发现的氯化芳香族化合物。本研究的目的是采用鱼类模型,在环境相关浓度下,对 PCA 相较于 PCP 的影响进行研究,以明确其对发育的作用。将斑马鱼胚胎分别暴露于 0.1、1、10、100、500、1000μg/L 的 PCA 和 PCP 中 96 小时。畸形观察、受精后 96 小时的存活率 LC50 测试和 72 小时孵化率 EC50 测试表明,PCP 的发育毒性大约是 PCA 的 15 倍。10μg/L 的 PCP 暴露导致 3,3',5-三碘甲状腺原氨酸(T3)水平升高,甲状腺素(T4)水平降低,而 PCA 对 T3 或 T4 水平没有影响。1μg/L 和 10μg/L 的 PCP 和 PCA 暴露表现出类似 T3 的可能甲状腺功能亢进效应,这是由于突触蛋白 I(SYN)、甲状腺素脱碘酶 III(Dio3)、甲状腺激素受体α a(THRαa)和甲状腺激素受体β(THRβ)的相对 mRNA 表达增加,以及甲状腺素脱碘酶 II(Dio2)的表达降低所致。结果表明,PCA 和 PCP 暴露均会导致形态畸形,可能影响中枢神经系统发育的时间和协调性,并通过破坏甲状腺激素调节途径来改变甲状腺激素水平。然而,PCA 的发育毒性至少比 PCP 低十倍。我们关于 PCA 和 PCP 的相对发育毒性及其潜在机制的结果,将有助于支持对人类群体中观察到的环境浓度和体内负荷水平的解释。

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