Role of Environmental Weathering and Gastrointestinal Digestion on the Bioavailability and Toxicity of Microplastic and Cadmium Mixtures - A Platform for Undergraduate Interdisciplinary Training

项目摘要 微塑料（MP）代表了一种新的人类健康危害，无论是作为直接的环境污染物 或作为其它混合污染物的组分。环境中的微塑料暴露在紫外线下 辐射（UV）改变它们的化学、形态组成和反应性。微塑料经常 与其它重金属相互作用（例如，镉（Cd）污染的水生系统。鱼不断地 通过意外摄入直接暴露于紫外线降解的MP，或间接暴露于被 宪兵。人类主要通过摄入受污染的食物和水接触MP。议员的命运 在消化过程中，很大程度上是未知的。推进我们对议员健康风险理解的关键障碍 缺乏将MP的环境化学转化与MP的生物累积联系起来的信息， 具体的健康影响。我们的总体目标是让本科研究人员参与跨学科的研究， 环境工程和毒理学项目，目标是MP转型的关键知识缺口， 反应性，生物利用度和毒性，以培养本科生的一套强大的技能， 鼓励追求研究生学位和STEM职业。总体目标是使用可量化的 方法和创新工具，以更好地了解环境风化和胃肠道的作用， 消化的生物利用度和毒性的MP和MP和镉的混合物。我们假设 MP的紫外线风化增加了遗留污染物的吸附（即，Cd）和胃肠道过程 影响其在肠上皮的生物利用度和毒性。此外，考虑到议员们在 通过内吞作用，我们认为MP可以干扰内体和溶酶体功能，特别是影响 必需微量金属代谢为了验证这一假设，我们提出了以下相互关联的目标： 具体目标1：评估紫外老化的微米和纳米塑料的转化和反应性， 淡水、商业矿泉水和胃肠（GI）液（即，具体目标2： MPs和MPs/Cd混合物在鱼肠道细胞中的生物有效性和急性毒性评价 RTgutGC细胞和人Caco-2细胞。目的2的目标是调查MP类型（大小）之间的联系 和组合物）和化学修饰（目的1）对MP单独或与 与Cd结合。具体目标3：评估MP对肠细胞的生理影响：使用数据 从目标1中，我们将选择具有更高反应性和吸附能力的MP，并使用目标2中的数据， 选择亚毒性但可检测剂量的MP和MP/Cd混合物，并评估其对必需微量元素的影响 金属稳态和代谢。我们的研究结果将有助于弥合化学之间的知识差距 MPs在环境中的转化以及对鱼类和人类健康的影响。我们的项目将作为 一个将本科生融入多学科研究的平台，并使他们能够获得 从环境化学到细胞生物学和毒理学的多种技能。

Project Summary Microplastics (MPs) represent an emerging human health hazard as either a direct environmental contaminant or as a component of other mixed pollutants. Microplastics in the environment are exposed to ultraviolet radiation (UV) that change their chemical, morphological composition, and reactivity. Microplastics frequently interact with other heavy metals (e.g., cadmium (Cd)) in contaminated aquatic systems. Fish are continuously exposed to UV-degraded MPs directly by accidental ingestion or indirectly by ingesting pray contaminated with MPs. Humans are mainly exposed to MPs via ingestion of contaminated food and water. The fate of MPs during digestion is largely unknown. The key barrier to advancing our understanding of the health risk of MPs is a lack of information linking MPs’ environmental chemical transformations with bioaccumulation of MPs, and specific health impacts. Our overall goal is to involve undergraduate researchers in an interdisciplinary environmental engineering and toxicology project that targets key knowledge gaps of MP transformation, reactivity, bioavailability, and toxicity to develop a strong set of skills in undergraduate students that encourages to pursue a graduate degree and career in STEM. The overarching objective is to use quantifiable approaches and innovative tools to better understand the role of environmental weathering and gastrointestinal digestion on the bioavailability and toxicity of MPs and MPs and cadmium mixtures. We hypothesize that ultraviolet weathering of MPs increases sorption of legacy pollutants (i.e., Cd) and gastrointestinal processes affect their bioavailability and toxicity at the intestinal epithelium. Moreover, considering that MPs are taken up via endocytosis we propose that MPs can interfere with endosome and lysosome function, specifically affecting essential trace metal metabolism. To test this hypothesis, we propose the following interconnected aims: Specific Aim 1: Evaluate the transformation and reactivity of ultraviolet-aged micro- and nanoplastics in freshwater, commercial mineral water, and gastrointestinal (GI) fluids (i.e., during digestion); Specific Aim 2: Evaluate the bioavailability and acute toxicity of MPs and MPs/Cd mixtures in intestinal cells form fish RTgutGC cells, and human Caco-2 cells. The goal of aim 2 is to investigate the link between MPs type (size and composition) and chemical modifications (aim 1) to bioavailability and acute toxicity of MPs alone or in combination with Cd. Specific Aim 3: Evaluate the physiological impact of MPs on intestinal cells: using data from aim 1 we will select MPs with higher reactivity and sorption capability and using data from aim 2 we will select subtoxic but detectable doses of MPs and MPs/Cd mixtures and evaluate their impact on essential trace metal homeostasis and metabolism. Our results will contribute to bridge the knowledge gap between chemical transformations of MPs in the environment and implications on fish and human health. Our project will serve as a platform for integrating undergraduate students into multidisciplinary research and will allow them to acquire multiple skills spanning from environmental chemistry to cell biology and toxicology.