<br>两类新兴二恶英类化合物的遗传依赖性发育毒理学的同类变异,Environmental Science & Technology

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两类新兴二恶英类化合物的遗传依赖性发育毒理学的同类变异
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2023-12-11 , DOI: 10.1021/acs.est.3c05622
Yishan Lin ₁ , Xueyi Li ₁ , Shaoqing Zhang ₁ , Qinyu Yang ₁ , Rui Zhang ₂ , Xiaowei Zhang _{1,

3}

Affiliation

新兴类别的二恶英类化合物 (DLC)，如羟基化/甲氧基化多溴二苯醚 (HO-/MeO-PBDE) 和多氯二苯硫醚 (PCDPS) 可能会对人类和野生动物造成多种不良后果，但其分子生物学方面存在知识差距。与早期生命环境暴露后不同结构相关的机制。这项研究整合了基因敲除技术和浓度依赖性减少斑马鱼转录组方法 (CRZT)，以揭示四种 H2O-/MeO-PBDE 和五种 PCDPS 在环境相关剂量下的发育毒性的毒理学途径。一般来说，芳烃受体 (AhR) 对 HO-PBDE 和 PCDPS 诱导的胚胎毒性和转录组效力的依赖性在不同同源物中有所不同。在 CRZT 测试中，敲除ahr2基因可使 DLC 诱导的胚胎毒性降低 1.02 至 76.48 倍，并降低基于转录组的效力 1.38 至 2124.74 倍。随着 MeO-PBDE 和 PCDPS 氯化程度的增加，表示 AhR 介导电位的倍数变化显着增加 ( p < 0.05)。此外， ahr2敲除主要影响 DLC 诱导的与 DNA 损伤、酶激活和器官发育相关的早期分子反应。我们的综合方法揭示了 AhR 在介导环境相关剂量下具有不同结构的新兴 DLC 的发育毒性方面的不同作用。

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Congener Variation of Genetic Dependent-Developmental Toxicology in Two Emerging Classes of Dioxin-like Compounds

Emerging classes of dioxin-like compounds (DLCs) like hydroxylated/methoxylated polybrominated diphenyl ethers (HO-/MeO-PBDEs) and polychlorinated diphenyl sulfides (PCDPSs) could lead to diverse adverse outcomes in humans and wildlife, yet knowledge gaps exist in their molecular mechanisms associated with different structures following early life environmental exposure. This study integrated a genetic knockout technique and concentration-dependent reduced zebrafish transcriptome approach (CRZT) to unravel the toxicological pathways underpinning developmental toxicity of four HO-/MeO-PBDEs and five PCDPSs at environmentally relevant doses. Generally, the dependence of aryl hydrocarbon receptor (AhR) on the embryotoxicity and transcriptomic potencies induced by the HO-PBDEs and PCDPSs varied across different congeners. The knockout of the ahr2 gene led to 1.02- to 76.48-fold decreases of DLC-induced embryotoxicities and reduced the transcriptome-based potencies ranging from 1.38 to 2124.74 folds in the CRZT test. The fold changes denoting AhR-mediated potentials significantly increased with the increasing chlorination degrees of MeO-PBDEs and PCDPSs (p < 0.05). Moreover, ahr2 knockout primarily affected the DLC-induced early molecular responses relevant to DNA damage, enzyme activation, and organ development. Our integrated approach revealed the differential role of AhR in mediating the developmental toxicity of emerging DLCs possessing varied structures at environmentally relevant doses.

更新日期：2023-12-11

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