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多溴联苯醚对广域斑海豚成纤维细胞系有遗传毒性作用。

Polybrominated diphenyl ethers exert genotoxic effects in pantropic spotted dolphin fibroblast cell lines.

机构信息

Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine Science, Shantou University, Shantou, Guangdong, 515063, China; Faculty of Veterinary and Animal Sciences, Lasbela University of Agriculture, Water and Marine Sciences, Uthal, Balochistan, Pakistan.

Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine Science, Shantou University, Shantou, Guangdong, 515063, China.

出版信息

Environ Pollut. 2021 Feb 15;271:116131. doi: 10.1016/j.envpol.2020.116131. Epub 2020 Dec 1.

DOI:10.1016/j.envpol.2020.116131
PMID:33412449
Abstract

Cetaceans accumulate persistent and toxic substances such as polybrominated diphenyl ethers in their tissue. PBDEs are ubiquitous in marine environments, and their exposure to mammals is linked to numerous health effects such as endocrine disruption, neurotoxicity, carcinogenicity, and fetal toxicity. However, the toxicological effects and mechanism of toxicity in cetaceans remains poorly understood. The effects of BDE-47 (0.1-0.5 μg mL), BDE-100 (0.1-0.5 μg mL), and BDE-209 (0.25-1.0 μg mL) exposure on cell viability, oxidative stress, mitochondrial structure, and apoptosis were evaluated using a recently established pantropical spotted dolphin (Stenella attenuata) skin fibroblast cell line (PSD-LWHT) as an in vitro model. However, the production of reactive oxygen species (ROS) increased following exposure to 1.0 μg mL PBDE while superoxide anion, hydroxyl radicals, and inducible nitric oxide increased in a dose-dependent manner. At 0.5-1.0 μg mL, PBDEs significantly reduced the mitochondrial membrane potential. In addition, exposure to BDE-47 and -209 significantly affected mitochondrial structure as well as cell signaling and transduction compared to BDE-100. Although PBDE exposure did not affect cell viability, a significant increase in cell apoptosis markers (Bcl2 and caspase-9) was observed. This study demonstrated that BDE-47, -100, and -209 congeners might cause cytotoxic and genotoxic effects as they play a crucial role in the dysregulation of oxidative stress and alteration of mitochondrial and cell membrane structure and activity in the fibroblast cells. Hence, these results suggest that PBDEs might have adverse health effects on cetaceans inhabiting contaminated marine environments.

摘要

鲸目动物在其组织中积累持久性和有毒物质,如多溴二苯醚。多溴二苯醚在海洋环境中无处不在,其暴露于哺乳动物与许多健康影响有关,如内分泌干扰、神经毒性、致癌性和胎儿毒性。然而,鲸目动物的毒性作用和毒性机制仍知之甚少。本研究采用最近建立的泛热带斑点海豚(Stenella attenuata)皮肤成纤维细胞系(PSD-LWHT)作为体外模型,评估了 BDE-47(0.1-0.5μg/mL)、BDE-100(0.1-0.5μg/mL)和 BDE-209(0.25-1.0μg/mL)暴露对细胞活力、氧化应激、线粒体结构和细胞凋亡的影响。然而,1.0μg/mL PBDE 暴露后活性氧(ROS)的产生增加,而过氧化物阴离子、羟自由基和诱导型一氧化氮则呈剂量依赖性增加。在 0.5-1.0μg/mL 时,PBDEs 显著降低了线粒体膜电位。此外,与 BDE-100 相比,BDE-47 和 BDE-209 暴露显著影响线粒体结构以及细胞信号转导和转导。尽管 PBDE 暴露并未影响细胞活力,但观察到细胞凋亡标志物(Bcl2 和 caspase-9)显著增加。本研究表明,BDE-47、BDE-100 和 BDE-209 同系物可能会产生细胞毒性和遗传毒性作用,因为它们在氧化应激失调以及线粒体和细胞膜结构和功能改变中发挥关键作用。因此,这些结果表明,PBDEs 可能对生活在受污染海洋环境中的鲸目动物产生不良健康影响。

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