Project 3: Toxicology of Petrogenic PAH in the Gulf Oil Spill

墨西哥湾漏油事故中成岩性多环芳烃的毒理学研究生成石油的多环芳烃(PAH)被认为是与墨西哥湾漏油事件有关的主要长期人类健康危害，因为通过食物链、皮肤接触和可能受到污染的水进行长期接触。GC-HARMS联盟的总体主题是了解和传达接触潜在危险的食源性多环芳烃对人类健康的风险。目前我们对多环芳烃的毒理学研究大多是通过对具有代表性的多环芳烃苯并[a]芘(B[a]P)的研究而获得的，苯并[a]芘是一种多器官、多物种的致癌物，也是已知的人类致癌物。因此，美国环保局将B[a]P列为其在食物链中监测的16种优先多环芳烃污染物之一。然而，苯并[a]磷和其他优先的多环芳烃污染物不是原油的主要成分。事实上，原油的多环芳烃组成复杂，含有多环芳烃混合物，我们对其毒理学数据知之甚少。因此，在缺乏进一步信息的情况下，无法进行基于苯并[a]磷毒性当量商(TEO)的风险评估。二 成岩多环芳烃种类丰富，包括广泛烷基化的多环芳烃和与原油风化有关的含氧多环芳烃。我们假设烷基化的多环芳烃将在其烷烃侧链上进行羟基化，然后通过硫酸盐化进行活化。我们还假设，氧化的多环芳烃可能通过广泛的氧化还原循环而调节它们的影响，从而导致活性氧物种(ROS)的产生。我们的目标是表征成岩性多环芳烃的代谢和毒性。我们的实验室在使用最先进的技术研究多环芳烃代谢、多环芳烃毒性和氧合多环芳烃方面拥有丰富的经验。 方法论。我们的具体目标如下。目的1将使用基于细胞的暴露和效应生物标志物(Elferink)来确定选定的烷基化和氧化的多环芳烃和多环芳烃提取物的相对效力。目的2将阐明具有代表性的烷基化和含氧多环芳烃(Penning)的代谢。目标3旨在确定含氧成岩多环芳烃是否会引起氧化应激损伤(Penning)，目标4将确定烷基化和含氧成岩化合物的致突变性 PAH(宾宁)。

Toxicology of Petrogenic PAH in the Gulf Oil Spill. Petrogenic Polycyclic Aromatic Hydrocarbons (PAH) are believed to be the major long-term human health hazard associated with the gulf-oil spill due to chronic exposure through the food chain, dermal contact and possibly contaminated water. The overall theme of the GC-HARMS consortium is to understand and communicate the human health risks of exposure to potentially hazardous food-borne petrogenic PAH. Most of what we currently know about the toxicology of PAH has been learned from studying the representative PAH, benzo[a]pyrene (B[a]P) which is a multi-organ and multi-species carcinogen and known human carcinogen. As a result, US-EPA includes B[a]P as one of its 16 priority PAH pollutants that it monitors in the food chain. However, B[a]P and the other priority PAH pollutants are not major components of crude-oil. In fact, the PAH composition of crude oil is complex and contains PAH mixtures for which we have little to know toxicological data. Thus risk assessment based on the B[a]P toxicity equivalency quotient (TEO) cannot be performed in the absence of further information. Two classes of petrogenic PAH are abundant and these are the extensively alkylated PAH and the oxygenated PAH associated with crude oil weathering. We hypothesize that alkylated PAH will be hydroxylated on their alkane side chains, followed by activation via sulfation. We also hypothesize that the oxygenated PAH may mediate their effects via extensive redox-cycling leading to the generation of reactive oxygen species (ROS). Our goal is to characterize the metabolism and toxicity of the petrogenic PAH species. Our laboratories have extensive experience in studying PAH-metabolism, PAH-toxicity, and oxygenated PAH using state-of-the art methodologies. Our specific aims are as follows. Aim 1 will determine the relative potency of selected alkylated and oxygenated petrogenic PAH and PAH extracts using cell-based exposure and effect biomarkers (Elferink). Aim 2 will elucidate the metabolism of representative alkylated and oxygenated petrogenic PAH (Penning). Aim 3 seeks to determine whether oxygenated petrogenic PAH causes oxidative stress injury (Penning), and Aim 4 will determine the mutagenicity of alkylated and oxygenated petrogenic PAH (Penning).