Immunotoxic and cellular mechanisms of action of petrogenic compounds

我们的社会在很大程度上仍然依赖化石燃料。随之而来的是与石油化工产品的提取、提炼、运输和使用相关的风险因素。当在与石油物质有关的环境中观察到对鱼类和野生动物的影响时，确定影响的原因存在挑战。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。原因是石油混合物极其复杂，含有成千上万种化合物，其中大多数成分所造成的危害尚不清楚。当鱼类接触到石化物质时，已观察到感染的发生率增加。一般认为，混合物中的化学制剂会导致免疫抑制，使细菌和病毒更容易感染生物体。本研究拟研究石油混合物中发现的两类化合物环烷酸和多环芳烃对鱼类免疫系统的影响。由于使用活生物体筛选大量化合物非常困难和昂贵，因此本研究建议开发使用鱼类免疫组织的细胞方法。这将通过从虹鳟鱼的血液中分离出主要种类的白细胞，并将细胞暴露于化学物质中来进行。这将检验这些化合物通过一种被称为程序性细胞死亡的现象影响细胞的假设。当细胞受到的损伤达到不能再恢复的程度时，这是细胞回收其内容物的方式。这项研究将检验这两类化合物可能对免疫细胞产生毒性的机制。此外，将对油砂作业的水和沉积物进行研究，以确定从鱼类免疫系统分离出来的细胞中产生毒性的物质。预计从这项研究中，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，并确定它们这样做的机制。这很重要，因为如果我们想诊断环境中发生的影响，一种化学诱发的疾病状态，我们必须知道这些影响的症状。在评价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/或生物种群的崩溃，也是有益的。加拿大在矿物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，特别是在水生系统方面，也是一个革新者，所获得的新知识将向全球输出。

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.