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使用人角质形成细胞对壬基酚和壬基酚聚乙氧基化物进行比较毒理学评估。

Comparative toxicological evaluation of nonylphenol and nonylphenol polyethoxylates using human keratinocytes.

作者信息

Kim Hyungjoo, Oh Sunhwa, Gye Myung Chan, Shin Incheol

机构信息

a Department of Life Science , Hanyang University , Seoul , Korea.

b Natural Science Institute , Hanyang University , Seoul , Korea.

出版信息

Drug Chem Toxicol. 2018 Oct;41(4):486-491. doi: 10.1080/01480545.2017.1391829. Epub 2017 Nov 10.

Abstract

Nonylphenol polyethoxylates (NPEOs) are a major group of nonionic surfactants widely used in various detergents, cleaners, plastics, papers, and agro-chemical products. Nonylphenol (NP), which is a final degraded metabolite derived from NPEOs, has been reported as an endocrine disrupter, known to mimic or disturb reproductive hormone functions. Concern about the hazards of NP and NPEOs has generated legal restrictions and action plans worldwide. Considering the fact that NP and NPEOs are majorly used in the production of products such as detergents, shampoos, and cosmetics which frequently come into contact with the skin, we investigated the effects of NP and NPEOs on a human keratinocyte cell line (HaCaT). In this study, the toxicity of NP and NPEOs was screened in HaCaT cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide thiazolyl blue assay and Western blotting. The potential cytotoxicity of substitutes was assessed by dose-response assays, relative cell viability, and genotoxicity caused by specific alterations in DNA damage response proteins (including ataxia-telangiectasia mutated, p53, Chk1, Chk2, and Histone H2A.X). We demonstrated that NP and NPEOs are toxic to HaCaT cells, as revealed by the decreased cell viability after 24 h treatment. NPs and NPEOs also induced apoptosis and DNA damage as shown by the activation of Poly(ADP-ribose) polymerase, Caspase-3, and Histone H2A.X.

摘要

壬基酚聚氧乙烯醚(NPEOs)是一类主要的非离子表面活性剂,广泛应用于各种洗涤剂、清洁剂、塑料、纸张和农用化学品中。壬基酚(NP)是NPEOs的最终降解代谢产物,据报道是一种内分泌干扰物,已知会模拟或干扰生殖激素功能。对NP和NPEOs危害的担忧已在全球范围内产生了法律限制和行动计划。鉴于NP和NPEOs主要用于生产经常与皮肤接触的洗涤剂、洗发水和化妆品等产品,我们研究了NP和NPEOs对人角质形成细胞系(HaCaT)的影响。在本研究中,使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐噻唑蓝试验和蛋白质免疫印迹法在HaCaT细胞中筛选了NP和NPEOs的毒性。通过剂量反应试验、相对细胞活力以及由DNA损伤反应蛋白(包括共济失调毛细血管扩张突变蛋白、p53、Chk1、Chk2和组蛋白H2A.X)的特定改变引起的遗传毒性来评估替代品的潜在细胞毒性。我们证明,NP和NPEOs对HaCaT细胞有毒性,24小时处理后细胞活力下降即表明了这一点。NP和NPEOs还诱导了细胞凋亡和DNA损伤,聚(ADP-核糖)聚合酶、半胱天冬酶-3和组蛋白H2A.X的激活即表明了这一点。

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