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两种原位化学还原生成的脱氯氯丹衍生物与母体化合物相比,没有遗传毒性和致突变性,且具有较低的促血管生成特性。

Two dechlorinated chlordecone derivatives formed by in situ chemical reduction are devoid of genotoxicity and mutagenicity and have lower proangiogenic properties compared to the parent compound.

机构信息

UFR Santé, Département Pharmacie, Université Bretagne Loire, Université d'Angers, 16 Bd Daviers, 49 100, Angers, France.

Institut Pasteur de Lille (IPL), Lille Cedex, France.

出版信息

Environ Sci Pollut Res Int. 2018 May;25(15):14313-14323. doi: 10.1007/s11356-017-8592-6. Epub 2017 Feb 16.

Abstract

Chlordecone (CLD) is a chlorinated hydrocarbon insecticide, now classified as a persistent organic pollutant. Several studies have previously reported that chronic exposure to CLD leads to hepatotoxicity, neurotoxicity, raises early child development and pregnancy complications, and increases the risk of liver and prostate cancer. In situ chemical reduction (ISCR) has been identified as a possible way for the remediation of soils contaminated by CLD. In the present study, the objectives were (i) to evaluate the genotoxicity and the mutagenicity of two CLD metabolites formed by ISCR, CLD-5a-hydro, or CLD-5-hydro (5a- or 5- according to CAS nomenclature; CLD-1Cl) and tri-hydroCLD (CLD-3Cl), and (ii) to explore the angiogenic properties of these molecules. Mutagenicity and genotoxicity were investigated using the Ames's technique on Salmonella typhimurium and the in vitro micronucleus micromethod with TK6 human lymphoblastoid cells. The proangiogenic properties were evaluated on the in vitro capillary network formation of human primary endothelial cells. Like CLD, the dechlorinated derivatives of CLD studied were devoid of genotoxic and mutagenic activity. In the assay targeting angiogenic properties, significantly lower microvessel lengths formed by endothelial cells were observed for the CLD-3Cl-treated cells compared to the CLD-treated cells for two of the three tested concentrations. These results suggest that dechlorinated CLD derivatives are devoid of mutagenicity and genotoxicity and have lower proangiogenic properties than CLD.

摘要

氯丹(CLD)是一种氯化烃杀虫剂,现被归类为持久性有机污染物。先前有几项研究报告称,慢性暴露于 CLD 会导致肝毒性、神经毒性、增加儿童早期发育和妊娠并发症的风险,并增加患肝癌和前列腺癌的风险。原位化学还原(ISCR)已被确定为修复 CLD 污染土壤的一种可行方法。在本研究中,目的是(i)评估由 ISCR 形成的两种 CLD 代谢物,即 CLD-5a-羟或 CLD-5-羟(根据 CAS 命名法分别为 5a-或 5-;CLD-1Cl)和三羟 CLD(CLD-3Cl)的遗传毒性和致突变性,以及(ii)探索这些分子的血管生成特性。使用沙门氏菌 typhimurium 的 Ames 技术和 TK6 人淋巴母细胞的体外微核微核方法研究了致突变性和遗传毒性。在体外人原代内皮细胞毛细血管网络形成试验中评估了促血管生成特性。与 CLD 一样,所研究的 CLD 的脱氯衍生物缺乏遗传毒性和致突变活性。在针对血管生成特性的测定中,与 CLD 处理的细胞相比,CLD-3Cl 处理的细胞的微血管长度明显较短,对于三种测试浓度中的两种浓度。这些结果表明,脱氯 CLD 衍生物缺乏致突变性和遗传毒性,并且比 CLD 具有更低的促血管生成特性。

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