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 作为一种直接的环境污染物，微塑料(Mps)是一种新出现的对人类健康的危害。 或作为其他混合污染物的组成部分。环境中的微塑料暴露在紫外线下 改变其化学成分、形态组成和反应性的辐射(UV)。经常使用微塑料 与受污染的水生系统中的其他重金属(例如，镉)相互作用。鱼一直在不停地 通过意外摄取或间接摄取受污染的PERE直接暴露于紫外线降解的MPS 国会议员。人类主要通过摄入受污染的食物和水而接触到MPS。下院议员的命运 消化过程在很大程度上是未知的。提高我们对MPS健康风险的认识的关键障碍 缺乏将MPS的环境化学转化与MPS的生物积累联系起来的信息，以及 具体的健康影响。我们的总体目标是让本科生研究人员参与一个跨学科的 针对MP转化的关键知识缺口的环境工程和毒理学项目， 反应性、生物利用度和毒性，以在本科生中培养一套强大的技能， 鼓励在STEM攻读研究生学位和职业生涯。首要目标是使用可量化的 更好地了解环境风化和胃肠道的作用的方法和创新工具 消化对MPS和MPS与镉混合物的生物利用度和毒性的影响。我们假设 MPS的紫外线老化增加了对遗留污染物(即Cd)的吸附和胃肠道过程 影响其在肠道上皮的生物利用度和毒性。此外，考虑到MPS被占用 通过内吞作用，我们认为MPS可以干扰内小体和溶酶体的功能，特别是影响 必需的微量金属代谢。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：评价紫外线老化微纳米塑料的转化和反应活性 淡水、商用矿泉水和胃肠道(GI)液(即在消化过程中)；具体目标2： MPS和MPS/CD混合物在鱼肠道细胞中的生物利用度和急性毒性评价 RTgutGC细胞和人Caco-2细胞。目标2的目标是调查MPS类型(大小 和组合物)和化学修饰(目标1)对MPS的生物利用度和急性毒性 与CD相结合。具体目标3：使用数据评估MPS对肠道细胞的生理影响 我们将从目标1中选择具有更高反应性和吸附能力的MPS，并使用目标2的数据，我们将 选择亚毒性但可检测剂量的MPS和MPS/Cd混合物，并评估其对基本痕量的影响 金属动态平衡和新陈代谢。我们的成果将有助于弥合化学和化学之间的知识鸿沟 多氯联苯在环境中的变化及其对鱼类和人类健康的影响。我们的项目将作为 一个将本科生整合到多学科研究的平台，并将允许他们获得 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.