Department of Mechanical Engineering and Materials Science, Duke University, Durham, North Carolina 27708, United States.
Chem Res Toxicol. 2020 Nov 16;33(11):2872-2879. doi: 10.1021/acs.chemrestox.0c00331. Epub 2020 Oct 16.
Titanium dioxide (TiO) particles are a common ingredient in food, providing the bright white color for many candies, gums, and frostings. While ingestion of these materials has been examined previously, few studies have examined the effect of these particles on lung cells. Inhalation is an important exposure pathway for workers processing these foods and, more recently, home users who purchase these particles directly. We examine the response of lung cells to food-grade TiO particles using a combination of fluorescence microscopy and RT-PCR. These experiments show that TiO particles generate intracellular reactive oxygen species, specifically superoxide, and alter expression of two epigenetic modifiers, histone deacetylase 9 (HDAC9) and HDAC10. We use a protein corona formed from superoxide dismutase (SOD), an enzyme that scavenges superoxide, to probe the relationship between TiO particles and superoxide generation. These experiments show that low, non-cytotoxic, concentrations of food-grade TiO particles lead to cellular responses, including altering two enzymes responsible for epigenetic modifications. This production of superoxide and change in epigenetic modifiers could affect human health following inhalation. We expect this research will motivate future in vivo experiments examining the pulmonary response to food-grade TiO particles.
二氧化钛（TiO）颗粒是食品中常见的成分，为许多糖果、口香糖和糖霜提供了明亮的白色。虽然以前已经研究过这些物质的摄入，但很少有研究检查这些颗粒对肺细胞的影响。对于加工这些食品的工人以及最近直接购买这些颗粒的家庭用户来说，吸入是一种重要的暴露途径。我们使用荧光显微镜和 RT-PCR 组合检查了肺细胞对食品级 TiO 颗粒的反应。这些实验表明，TiO 颗粒会产生细胞内活性氧物质，特别是超氧阴离子，并改变两种表观遗传修饰剂的表达，组蛋白去乙酰化酶 9（HDAC9）和 HDAC10。我们使用超氧化物歧化酶（SOD）形成的蛋白质冠，一种清除超氧阴离子的酶，来探究 TiO 颗粒与超氧阴离子生成之间的关系。这些实验表明，低浓度、非细胞毒性的食品级 TiO 颗粒会导致细胞反应，包括改变两种负责表观遗传修饰的酶。这种超氧阴离子的产生和表观遗传修饰剂的变化可能会影响吸入后人类的健康。我们预计这项研究将推动未来检查食品级 TiO 颗粒对肺部反应的体内实验。
