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经口给予食品级二氧化钛和植物炭颗粒后大鼠肺部的端粒长度和遗传毒性。

Telomere length and genotoxicity in the lung of rats following intragastric exposure to food-grade titanium dioxide and vegetable carbon particles.

机构信息

Department of Public Health, Section of Environmental Health, Frederiksberg C, Denmark.

Department of Drug Design and Pharmacology, Section of Molecular and Cellular Pharmacology, Frederiksberg C, Denmark.

出版信息

Mutagenesis. 2019 May 29;34(2):203-214. doi: 10.1093/mutage/gez003.

DOI:10.1093/mutage/gez003
PMID:30852617
Abstract

Vegetable carbon (E153) and titanium dioxide (E171) are widely used as black and white food colour additives. The aim of this study was to assess gastrointestinal tight junction and systemic genotoxic effects in rats following exposure to E153 and E171 for 10 weeks by oral gavage once a week. The expression of tight junction proteins was assessed in intestinal tissues. Levels of DNA strand breaks, oxidatively damaged DNA and telomere length were assessed in secondary organs. Hydrodynamic suspensions of E153 and E173 indicated mean particles sizes of 230 and 270 nm, respectively, and only E153 gave rise to intracellular production of reactive oxygen species in colon epithelial (Caco-2) cells. Rats exposed to E153 (6.4 mg/kg/week) or E171 (500 mg/kg/week) had decreased gene expression of the tight junction protein TJP1 (P < 0.05). E153 (6.4 mg/kg/week) also decreased OCLN (P < 0.05) in the colon and occludin protein expression in the small intestine (P < 0.05). Furthermore, E153 or E171 exposed rats had shorter telomeres in the lung (P < 0.05). Plasma from particle-exposed rats also produced telomere shortening in cultured lung epithelial cells. There were unaltered levels of oxidatively damaged DNA in the liver and lung and no changes in the DNA repair activity of oxidatively damaged DNA in the lung. Altogether, these results indicate that intragastric exposure to E153 and E171 is associated with reduced tight junction protein expression in the intestinal barrier and telomere length shortening in the lung in rats.

摘要

蔬菜炭黑(E153)和二氧化钛(E171)被广泛用作黑色和白色食品着色添加剂。本研究的目的是通过每周口服一次,评估 10 周后 E153 和 E171 暴露对大鼠胃肠道紧密连接和系统遗传毒性的影响。评估了肠道组织中紧密连接蛋白的表达。评估了次级器官中 DNA 链断裂、氧化损伤 DNA 和端粒长度的水平。E153 和 E173 的流体动力学悬浮液分别表明平均粒径为 230nm 和 270nm,只有 E153 会在结肠上皮(Caco-2)细胞中引起活性氧的细胞内产生。暴露于 E153(6.4mg/kg/周)或 E171(500mg/kg/周)的大鼠其紧密连接蛋白 TJP1 的基因表达降低(P<0.05)。E153(6.4mg/kg/周)还降低了结肠中的 OCLN(P<0.05)和小肠中的紧密连接蛋白表达(P<0.05)。此外,E153 或 E171 暴露的大鼠的肺中的端粒较短(P<0.05)。暴露于颗粒的大鼠的血浆也会导致培养的肺上皮细胞中端粒缩短。肝脏和肺部的氧化损伤 DNA 水平没有改变,肺部氧化损伤 DNA 的修复活性也没有改变。总之,这些结果表明,胃内暴露于 E153 和 E171 与大鼠肠道屏障中紧密连接蛋白表达降低和肺中端粒缩短有关。

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