Immunotoxic and cellular mechanisms of action of petrogenic compounds

成岩化合物的免疫毒性和细胞作用机制

• 批准号: RGPIN-2017-05535
• 负责人: vandenHeuvel, Michael
• 金额: $ 2.48万
• 依托单位: University of Prince Edward Island
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=667500
• 关键词: Immunotoxic; cellular; mechanisms; action; petrogenic

Our society is still largely dependent on fossil fuels. Accompanying that is an element of risk associated with the extraction, refining, transportation and use of petrochemicals. There are challenges in determining the cause of impacts on fish and wildlife when they are observed in the environment associated with petroleum substances. We are equally limited in our ability to predict those impacts when we attempt to determine the danger associated with activities such as pipelines. The reason for this is that petroleum mixtures are incredibly complex, containing tens of thousands of compounds and the hazard posed by most of those constituents remains unknown. When fishes are exposed to petrochemical substances, an increased incidence of infections has been observed. It is generally presumed that chemical agents in the mixtures cause immune suppression, allowing bacteria and viruses to infect the organism more easily. This research proposes to study two classes of compounds, naphthenic acids and polycyclic aromatic hydrocarbons found in petroleum mixtures, for their ability to impact the immune system of fishes. As it is prohibitively difficult and expensive to screen large numbers of compounds using live organisms, this research proposes to develop cellular methods using the immune tissue of fishes. This will be conducted by separating the major classes of white blood cells from the blood of rainbow trout and exposing the cells to chemicals. This will test the hypothesis that these groups of compounds influence the cell by a phenomenon known as programmed cell death. This is the cells way of recycling its contents when the damage to a cell has reached a point where it can no longer recover. The research will examine the mechanisms by which these two classes of compounds might cause toxicity to immune cells. Further to this, research will be conducted on waters and sediments from oil sands operations in order to identify substances that cause toxicity to cells isolated from the fish immune system. It is anticipated that from this research we will gain an understanding of the ability of specific compounds in petrochemical mixtures to cause immune suppression and determine mechanisms by which they do so. This is important, because if we want to diagnose impacts that are occurring in the environment, a chemically-induced disease state, we must know the symptoms of those impacts. When evaluating the hazard of such compounds in the environment it is also informative to know if there is a danger of immune suppression, leading to disease and or collapses of populations of organisms. Canada is heavily invested in fossil fuel exploitation and this research is directly applicable to current activities in this sector. Canada has also been an innovator in environmental monitoring and assessment, particularly with regards to aquatic systems, and new knowledge gained will be exported globally.

我们的社会仍然在很大程度上依赖化石燃料。伴随而来的是与石化产品的开采、提炼、运输和使用相关的风险因素。在与石油物质有关的环境中观察到鱼类和野生动物时，在确定它们受到影响的原因方面存在挑战。当我们试图确定与管道等活动相关的危险时，我们预测这些影响的能力同样有限。其原因是，石油混合物极其复杂，含有数万种化合物，其中大多数成分构成的危险尚不清楚。当鱼暴露在石油化学物质中时，观察到感染的发生率增加。通常认为，混合物中的化学物质会导致免疫抑制，使细菌和病毒更容易感染有机体。这项研究建议研究石油混合物中发现的两类化合物，环烷酸和多环芳烃，以了解它们影响鱼类免疫系统的能力。由于使用活生物筛选大量化合物的难度和成本都高得令人望而却步，这项研究建议开发利用鱼类免疫组织的细胞方法。这将通过从虹鲑鱼的血液中分离出主要类别的白细胞，并将这些细胞暴露在化学物质中来进行。这将检验一种假设，即这些化合物通过一种被称为程序性细胞死亡的现象来影响细胞。这是当细胞受损到不能再恢复的程度时，细胞回收其内容物的方式。这项研究将研究这两类化合物可能对免疫细胞产生毒性的机制。此外，将对油砂作业产生的水域和沉积物进行研究，以确定对从鱼类免疫系统中分离出来的细胞产生毒性的物质。预计通过这项研究，我们将了解石化混合物中特定化合物引起免疫抑制的能力，并确定它们产生免疫抑制的机制。这一点很重要，因为如果我们想要诊断发生在环境中的影响，一种化学诱导的疾病状态，我们必须知道这些影响的症状。在评估这类化合物在环境中的危害时，了解是否存在免疫抑制的危险，从而导致疾病和/或生物体种群的崩溃，也是有益的。加拿大在化石燃料开采方面投入了大量资金，这项研究直接适用于该部门目前的活动。加拿大在环境监测和评估方面也是创新者，特别是在水生系统方面，所获得的新知识将向全球输出。