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

用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型

基本信息

批准号：
10708517
负责人：
Jennifer Harr
金额：
$ 16.37万
依托单位：
ST. MARY'S UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10708517
关键词：
Affect Air Animal Model Animals Area Behavior Biological Biological Models Blood Caenorhabditis elegans Chemical Exposure Chemicals Chromosome Structures Consumption DNA Damage DNA Repair Data Defect Development Developmental Delay Disorders Dibutyl Phthalate Embryo Embryonic Induction Environment Environmental Health Experimental Models Exposure to Food Frequencies Genes Genome Stability Goals Health High Pressure Liquid Chromatography Human Impairment Individual Ingestion Insecticides Investigation Knowledge Laboratories Libraries Location Mammalian Cell Mammals Mass Spectrum Analysis Metabolism Methods Molecular Muscle Mutation Outcome Pathologic Pathway interactions Permethrin Pesticides Phase Phenotype Physiological Physiology Placenta Plasticizers Plastics Polystyrenes Productivity Protocols documentation Public Health Reporter Reproducibility Research Risk Source Sterility Students System Testing Time Tissues Toxic effect Toxicology Toxin Training Water Whole Organism absorption bioaccumulation biological systems cell motility delivery vehicle environmental chemical environmental chemical exposure environmental toxicology experience experimental study genome integrity genotoxicity human tissue in vivo innovation meter model organism novel particle phthalates pollutant prevent programs shear stress undergraduate research

Affect Air Animal Model Animals Area Behavior Biological Biological Models Blood Caenorhabditis elegans Chemical Exposure Chemicals Chromosome Structures Consumption DNA Damage DNA Repair Data Defect Development Developmental Delay Disorders Dibutyl Phthalate Embryo Embryonic Induction Environment Environmental Health Experimental Models Exposure to Food Frequencies Genes Genome Stability Goals Health High Pressure Liquid Chromatography Human Impairment Individual Ingestion Insecticides Investigation Knowledge Laboratories Libraries Location Mammalian Cell Mammals Mass Spectrum Analysis Metabolism Methods Molecular Muscle Mutation Outcome Pathologic Pathway interactions Permethrin Pesticides Phase Phenotype Physiological Physiology Placenta Plasticizers Plastics Polystyrenes Productivity Protocols documentation Public Health Reporter Reproducibility Research Risk Source Sterility Students System Testing Time Tissues Toxic effect Toxicology Toxin Training Water Whole Organism absorption bioaccumulation biological systems cell motility delivery vehicle environmental chemical environmental chemical exposure environmental toxicology experience experimental study genome integrity genotoxicity human tissue in vivo innovation meter model organism novel particle phthalates pollutant prevent programs shear stress undergraduate research

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项目摘要

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.

项目摘要/摘要微塑料（MP，塑料颗粒<5 mm）在环境中普遍存在，新兴健康忧虑。国会议员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，使其消费可能有害。国会议员几乎被发现所有人类组织，具体来说，纳米塑料（NP，≤1µm）由于能够进入的能力而令人震惊哺乳动物细胞。当前对纳米塑性污染物暴露的物理或病理作用的研究是有限的，单独摄入NP或与环境化学物质结合的人类风险尚不清楚。长期目标是了解NP暴露对生物系统的影响。总体目标该应用是（i）建立秀丽隐杆线虫（秀丽隐杆线虫）作为NP化学的新型模型系统混合研究和（ii）测试NP作为环境化学品的递送工具的能力和影响。中心假设是吸收环境化学物质的NP会促进DNA损伤以及随后的生理变化。该项目的理由是化学污染物等农药邻苯二甲酸盐是遗传毒性的，并集中在环境中的纳米塑料中。此外，模型诸如秀丽隐杆线虫之类的生物可以消耗NP，其中包含的化学物质被吸收动物。提出了两个具体目的来检验中心假设：1）确定DNA损伤效应 NP和吸收的环境化学品和2）确定NP和吸收的环境化学暴露。在第一个目标下，将建立协议以量化 NP中的化学吸收，并验证秀丽隐杆线虫中摄入化学物质的吸收和代谢。此外，我们将通过评估频率和使用已建立的基于荧光的记者的突变位置。为了第二个目标，秀丽隐杆线暴露了仅由于NP和化学物质而导致的已知物理缺陷，将观察到NP化学混合物，假设合并效应将更加严重。此外，我们将关联特定组织中的DNA损伤，在NP化学暴露后观察到的表型变化。这在应用程序的选项中，本应用程序中提出的研究具有创新性，因为它专注于系统以及评估和确定NP和环境化学的综合作用的严格方法体内和整个动物中细胞水平上的毒理学，目前尚不可用的系统。这拟议的研究很重要，因为预计它将为持续提供强大的科学依据为防止NP化学混合物暴露而导致的健康结果的研究，并将告知暴露纳米塑料和环境化学污染物的限制。最终，这种知识有可能极大地增加了我们对NP和环境化学物质的加性毒理学及其风险的理解对人类健康。