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未受管制的卤代芳香族水消毒副产物会对人胎盘细胞的内分泌和脂质代谢产生干扰作用。

Non-regulated haloaromatic water disinfection byproducts act as endocrine and lipid disrupters in human placental cells.

机构信息

Environmental Chemistry Department, IDAEA -CSIC-, C/ Jordi Girona, 18-26, 08034, Barcelona, Spain.

Technologies for Water Management and Treatment Research Group, Department of Civil Engineering, University of Granada, Avda Severo Ochoa s/n, Campus de Fuentenueva, Granada, 18071, Spain; Institute for Water Research (IdA), University of Granada, Ramón y Cajal 4, 18071, Granada, Spain.

出版信息

Environ Pollut. 2024 Feb 1;342:123092. doi: 10.1016/j.envpol.2023.123092. Epub 2023 Dec 9.

DOI:10.1016/j.envpol.2023.123092
PMID:38072025
Abstract

The disinfection of drinking water generates hundreds of disinfection byproducts (DBPs), including haloaromatic DBPs. These haloaromatic DBPs are suspected to be more toxic than haloaliphatic ones, and they are currently not regulated. This work investigates their toxicity and ability to interfere with estrogen synthesis in human placental JEG-3 cells, and their genotoxic potential in human alveolar A549 cells. Among the haloaromatic DBPs studied, halobenzoquinones (2,6-dichloro-1,4-benzoquinone (DCBQ) and 2,6-dibromo-1,4-benzoquinone (DBBQ)) showed the highest cytotoxicity (EC: 18-26 μg/mL). They induced the generation of very high levels of reactive oxygen species (ROS) and up-regulated the expression of genes involved in estrogen synthesis (cyp19a1, hsd17b1). Increased ROS was linked to significant depletion of polyunsaturated lipid species from inner cell membranes. The other DBPs tested showed low or no significant cytotoxicity (EC ≥ 100 μg/mL), while 2,4,6-trichloro-phenol (TCP), 2,4,6-tribromo-phenol (TBP) and 3,5-dibromo-4-hydroxybenzaldehyde (DCHB) induced the formation of micronuclei at concentrations much higher than those typically found in water (100 μg/mL). This study reveals the different modes of action of haloaromatic DBPs, and highlights the toxic potential of halobenzoquinones, which had a significant impact on the expression of placenta steroid metabolism related genes and induce oxidative stress, implying potential adverse health effects.

摘要

饮用水的消毒会产生数百种消毒副产物(DBPs),包括卤代芳香族 DBPs。这些卤代芳香族 DBPs 被怀疑比卤代脂肪族 DBPs 毒性更大,但目前尚未受到监管。本研究调查了它们在人胎盘 JEG-3 细胞中的毒性和对雌激素合成的干扰能力,以及在人肺泡 A549 细胞中的遗传毒性。在所研究的卤代芳香族 DBPs 中,卤代苯醌(2,6-二氯-1,4-苯醌(DCBQ)和 2,6-二溴-1,4-苯醌(DBBQ))表现出最高的细胞毒性(EC:18-26μg/mL)。它们诱导产生非常高水平的活性氧(ROS),并上调参与雌激素合成的基因的表达(cyp19a1,hsd17b1)。增加的 ROS 与内细胞膜中多不饱和脂质种类的明显耗竭有关。其他测试的 DBPs 表现出低或无明显的细胞毒性(EC≥100μg/mL),而 2,4,6-三氯苯酚(TCP)、2,4,6-三溴苯酚(TBP)和 3,5-二溴-4-羟基苯甲醛(DCHB)则在远高于水通常存在浓度(100μg/mL)的浓度下诱导微核形成。本研究揭示了卤代芳香族 DBPs 的不同作用模式,并强调了卤代苯醌的潜在毒性,它们对胎盘类固醇代谢相关基因的表达有显著影响,并诱导氧化应激,暗示可能对健康产生不利影响。

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