A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health

项目摘要/摘要 微塑料(MP，塑料颗粒5毫米)在环境中无处不在，是一种新兴的健康产品。 担忧。MPS有能力从环境中积累化学污染物，并有助于 污染物的生物积累，使其消费具有潜在的危险。国会议员已经在近几个地方被发现 所有人体组织，特别是纳米塑料(NPs，≤1微米)都令人担忧，因为它能够进入 哺乳动物细胞。纳米塑料污染物暴露的生理或病理效应研究现状 摄入NPs的风险是有限的，人类单独摄取NPs或与环境化学品结合的风险尚不清楚。 长期目标是了解NP暴露对生物系统的影响。年的总体目标 本应用的目的是：(1)建立秀丽线虫(C.elegans)作为NP-化工的新模式系统 混合研究和(Ii)测试NPs作为环境化学品运载工具的能力和影响。 中心假设是，吸收了环境化学物质的NPs将促进DNA损伤 以及随后的生理变化。这个项目的基本原理是像杀虫剂这样的化学污染物 邻苯二甲酸酯具有遗传毒性，在环境中会集中在纳米塑料中。此外，模型 线虫等生物可以消耗NPs，其中包含的化学物质被 动物。提出了两个特定的目标来检验中心假设：1)确定DNA损伤效应 NPS和吸收的环境化学品；2)确定NPs和 吸收环境中的化学物质暴露。在第一个目标下，将建立协议来量化 纳米粒子中的化学吸收，并验证线虫摄取的化学物质的吸收和代谢。 此外，我们将通过评估频率和频率来评估NP-化学混合物造成的DNA损伤 使用已建立的基于荧光的报告程序来定位突变。为了第二个目的，线虫暴露在 对于仅由NP和化学品引起的已知生理缺陷，将观察到NP-化学混合物， 假设综合效应将更加严重。此外，我们还会将 特定组织中的DNA损伤，并观察到NP化学物质暴露后的表型变化。这个 这项申请中提出的研究是创新的，由申请者选择，因为它侧重于系统性 以及评估和确定NP和环境化学品的综合影响的严格方法 在活体和整个动物的细胞水平上的毒理学，这是一个目前无法获得的系统。这个 拟议的研究意义重大，因为预计它将为继续 防止接触NP化学品混合物造成的负面健康后果的研究，并将通报暴露情况 对纳米塑料和环境化学污染物的限制。最终，这样的知识有可能 大大增加了我们对NPs和环境化学品的添加毒理学及其风险的了解 为人类健康干杯。

Project Summary/Abstract Microplastics (MP, plastic particles < 5 mm) are pervasive in the environment and an emerging health concern. MPs have the ability to accumulate chemical pollutants from the environment and contribute to bioaccumulation of pollutants, making their consumption potentially hazardous. MPs have been found in nearly all human tissue and specifically, nanoplastics (NPs, ≤ 1 µm) are of alarming concern due to the ability to enter mammalian cells. Current research into the physiological or pathological effects of nanoplastic pollutant exposure is limited, and the human risks of ingestion of NPs alone or combined with environmental chemicals are unknown. The long-term goal is to understand the impact of NP exposure on biological systems. The overall objectives in this application are to (i) establish Caenorhabditis elegans (C. elegans) as a novel model system for NP-chemical mixture research and (ii) to test the ability and impact of NPs as a delivery vehicle for environmental chemicals. The central hypothesis is that NPs, which have absorbed environmental chemicals, will promote DNA damage and subsequent changes in physiology. The rationale for this project is that chemical pollutants like pesticides and phthalates are genotoxic and become concentrated in nanoplastics in the environment. Furthermore, model organisms such as C. elegans can consume NPs and the chemicals contained in them are absorbed by the animal. Two specific aims are proposed to test the central hypothesis: 1) Determine DNA damaging effects of NPs and absorbed environmental chemicals and 2) Determine the physiological consequence of NPs and absorbed environmental chemical exposure. Under the first aim, protocols will be established to quantify chemical absorption in NPs, and to verify absorption and metabolism of ingested chemicals in C. elegans. Additionally, we will evaluate DNA damage induced by NP-chemical mixtures by assessing frequency and location of mutations using an established fluorescent-based reporter. For the second aim, C. elegans exposed to NP-chemical mixtures will be observed for known physiological defects due to the NPs and chemicals alone, with the hypothesis that combined effects will be more severe. Furthermore, we will correlate the presence of DNA damage in specific tissues, with the observed phenotypic changes after NP-chemical exposure. The research proposed in this application is innovative, in the applicant’s option, because it focuses on systematic and rigorous methods to assess and determine the combined effects of NP and environmental chemical toxicology on the cellular level in vivo and in a whole animal, a system that is currently not available. The proposed research is significant because it is expected to provide strong scientific justification for continued studies to prevent negative health outcomes due to NP-chemical mixture exposure and will inform exposure limits on nanoplastics and environmental chemical pollutants. Ultimately such knowledge has the potential to greatly add to our understanding of the additive toxicology of NPs and environmental chemicals and their risks to human health.