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低剂量三氯生和邻苯二甲酸二(2-乙基己基)酯及其组合暴露引起的急性毒性和DNA不稳定性

Acute Toxicity and DNA Instability Induced by Exposure to Low Doses of Triclosan and Phthalate DEHP, and Their Combinations, .

作者信息

Duarte Nathalia de Assis Aguilar, de Lima Lindiane Eloisa, Maraslis Flora Troina, Kundi Michael, Nunes Emilene Arusievicz, Barcelos Gustavo Rafael Mazzaron

机构信息

Department of Biosciences, Institute of Health and Society, Federal University of São Paulo, Santos, Brazil.

Institute of Environmental Health, Medical University of Vienna, Vienna, Austria.

出版信息

Front Genet. 2021 Apr 20;12:649845. doi: 10.3389/fgene.2021.649845. eCollection 2021.

Abstract

Triclosan (TCS) is an antimicrobial agent widely used in personal care products (PCP) and the di-(2-ethyl hydroxy-phthalate) (DEHP) is a chemical compound derived from phthalic acid, used in medical devices and plastic products with polyvinyl chloride (PVCs). As result of their extensive use, TCS and DEHP have been found in the environment and previous studies demonstrated the association between their exposure and toxic effects, mostly in aquatic organisms, but there is a shortage in the literature concerning the exposure of TCS and DEHP in human cells. The aim of the present study was to assess the impact of exposure to TCS and DEHP, as well as their combinations, on biomarkers related to acute toxicity and DNA instability, in HepG2 cells, by use of cytokinesis-block micronucleus cytome (CBMNCyt) assay. For that, the cultures were exposed to TCS, DEHP and combinations at doses of 0.10, 1.0, and 10 μM for the period of 4 h and the parameters related to DNA damage (i.e., frequencies of micronuclei (MN) and nuclear buds (NBUDs), to cell division (i.e., nuclear division index (NDI) and nuclear division cytotoxic index (NDCI) and to cell death (apoptotic and necrotic cells) were scored. Clear mutagenic effects were seen in cells treated with TCS, DEHP at doses of 1.0 and 10 μM, but no combined effects were observed when the cells were exposed to the combinations of TCS + DEHP. On the other hand, the combination of the toxicants significantly increased the frequencies of apoptotic and necrotic cells, as well as induced alterations of biomarkers related to cell viability (NDI and NDCI), when compared to the groups treated only with TCS or DEHP. Taken together, the results showed that TCS and DEHP are also able to induce acute toxicity and DNA damage in human cells.

摘要

三氯生(TCS)是一种广泛用于个人护理产品(PCP)的抗菌剂,而二(2-乙基羟基邻苯二甲酸酯)(DEHP)是一种由邻苯二甲酸衍生的化合物,用于医疗设备和聚氯乙烯(PVC)塑料制品。由于它们的广泛使用,环境中已发现三氯生和DEHP,先前的研究表明它们的暴露与毒性作用之间存在关联,主要是在水生生物中,但关于三氯生和DEHP在人类细胞中的暴露情况,文献中存在不足。本研究的目的是通过使用胞质分裂阻滞微核细胞组学(CBMNCyt)试验,评估暴露于三氯生和DEHP及其组合对HepG2细胞中与急性毒性和DNA不稳定性相关的生物标志物的影响。为此,将培养物暴露于浓度为0.10、1.0和10 μM的三氯生、DEHP及其组合中4小时,并对与DNA损伤相关的参数(即微核(MN)和核芽(NBUDs)的频率)、细胞分裂(即核分裂指数(NDI)和核分裂细胞毒性指数(NDCI))以及细胞死亡(凋亡和坏死细胞)进行评分。在用1.0和10 μM剂量的三氯生、DEHP处理的细胞中观察到明显的诱变作用,但当细胞暴露于三氯生+DEHP组合时未观察到联合作用。另一方面,与仅用三氯生或DEHP处理的组相比,毒物组合显著增加了凋亡和坏死细胞的频率,并诱导了与细胞活力相关的生物标志物(NDI和NDCI)的改变。综上所述,结果表明三氯生和DEHP也能够在人类细胞中诱导急性毒性和DNA损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79ad/8093768/ec9c6723fea9/fgene-12-649845-g001.jpg

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