Oxidant Exposure and Related Harm from Tobacco Smoke

烟草烟雾中的氧化剂暴露和相关危害

基本信息

批准号：
10191024
负责人：
Zachary T Bitzer
金额：
$ 44.83万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10191024
关键词：
Acrolein Activated Charcoal Address Aldehydes Barley Biological Markers C57BL/6 Mouse Carcinogens Cessation of life Charcoal Chemicals Chronic Disease Chronic Obstructive Airway Disease Cigar Cigarette Complex Mixtures Data Development Disease Electron Spin Resonance Spectroscopy Female Filtration Free Radicals Generations Health Inflammation Inhalation Liquid Chromatography Lung Lung Inflammation Malignant Neoplasms Measurement Methodology Methods Modeling Mus Nicotine Nose Oxidants Oxidative Stress Pathway interactions Phase Play Policies Reporting Role Smoke Smoker Smoking Smoking Behavior Surgeon Tars Tobacco Tobacco smoke Tobacco smoking behavior Tobacco use Toxic effect Toxicology Variant Work base chemical property cigarette smoke cigarette smoke-induced cold temperature combustible cigarette combustible tobacco design lung injury male method development mouse model novel marker oriental oxidative damage potential biomarker pulmonary function reconstitution tandem mass spectrometry tobacco exposure tobacco products tobacco regulatory science tobacco smoke exposure toxicant

项目摘要

Abstract Toxicity and negative health effects of tobacco smoking results from the inhalation of a complex mixture of over 7000 chemicals including many toxicants and carcinogens included on the FDA list of Harmful and Potentially Harmful Constituents (HPHCs). Oxidants are a major class of toxicant abundant in tobacco smoke and are thought to play a critical role in the development of tobacco related diseases including COPD, CVD and cancer through the generation of oxidative stress/damage and inflammation. However, the specific oxidants most responsible remain unclear. While several oxidants are included on the HPHC list (eg. carbonyls), one of the most reactive, damaging and abundant classes, free radicals, are not represented. Recently we found that delivery of radicals varied greatly (>12-fold) across cigarette brands, was substantially impacted by product design (e.g. tobacco variety) and smoking behaviors and was high in other popular combustible products including little filtered cigars. Radical delivery was also highly correlated with other oxidants including carbonyls (eg. acrolein). Based upon these findings, we propose that tobacco-derived oxidants, including free radicals, represent an important target for developing regulatory strategies aimed at reducing the harm from combustible tobacco use. This approach is strongly supported by our preliminary findings that levels of oxidative stress biomarkers are significantly reduced in smokers who switch from high to low oxidant cigarettes. The objectives of this project are to identify specific oxidants responsible for the generation of tobacco related harm and determine the impact of oxidant reduction on tobacco-related toxicity endpoints. To this end, we propose 3 specific aims. In Aim 1, we will determine the levels and identity of free radicals and other oxidants delivered by different combustible tobacco products/brands using advanced electron paramagnetic resonance (EPR) spectroscopy and liquid chromatography-tandem mass spectrometry (LC- MS/MS) methodologies. In Aim 2 we conduct exposure studies in a relevant mouse model to determine the impact of tobacco smoke oxidants on lung damage and inflammation; comparing effects of high vs. low oxidant brands and tobacco varieties. In Aim 3, we will conduct mouse exposure studies to determine the impact of charcoal filtration of cigarette smoke on oxidant-induced lung damage in the mouse. Overall, these studies will significantly contribute to the field of tobacco regulatory science by focusing on the toxicological importance of oxidant exposure. These data will be of particular value to the FDA for the development of regulatory policies aimed at reducing harm imposed by tobacco usage.

抽象的吸烟的毒性和对健康的负面影响是由于吸入过量的复杂混合物造成的。 FDA 有害和潜在清单中包含 7000 种化学物质，其中包括许多有毒物质和致癌物质有害成分 (HPHC)。氧化剂是烟草烟雾中含量丰富的一类主要有毒物质，人们认为在慢性阻塞性肺病、心血管疾病和癌症等烟草相关疾病的发展中发挥着关键作用通过氧化应激/损伤和炎症的产生。然而，特定氧化剂最责任仍不清楚。虽然 HPHC 列表中包含多种氧化剂（例如羰基化合物），但其中一种最活跃、最具破坏性和最丰富的类别——自由基——没有被代表。最近我们发现不同卷烟品牌的自由基传递差异很大（>12倍），很大程度上受到产品的影响设计（例如烟草品种）和吸烟行为，在其他流行的可燃产品中也很高包括少量过滤雪茄。自由基传递也与包括羰基在内的其他氧化剂高度相关（例如丙烯醛）。基于这些发现，我们提出烟草衍生的氧化剂，包括自由基，是制定旨在减少危害的监管战略的重要目标可燃烟草的使用。我们的初步发现强烈支持这种方法，即从高氧化剂转为低氧化剂的吸烟者的氧化应激生物标志物显着减少香烟。该项目的目标是确定负责产生烟草相关危害并确定氧化剂还原对烟草相关毒性终点的影响。到为此，我们提出3个具体目标。在目标 1 中，我们将确定自由基的水平和特性，以及不同可燃烟草产品/品牌使用先进电子提供的其他氧化剂顺磁共振 (EPR) 光谱和液相色谱-串联质谱 (LC- MS/MS) 方法。在目标 2 中，我们在相关小鼠模型中进行暴露研究，以确定烟草烟雾氧化剂对肺损伤和炎症的影响；比较高氧化剂与低氧化剂的效果品牌和烟草品种。在目标 3 中，我们将进行小鼠暴露研究以确定香烟烟雾的木炭过滤对氧化剂引起的小鼠肺损伤的影响。总体而言，这些研究将通过关注烟草毒理学的重要性，为烟草监管科学领域做出了重大贡献氧化剂暴露。这些数据对于 FDA 制定监管政策具有特别价值旨在减少烟草使用造成的危害。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

An Integrated Approach for Preventing Oral Cavity and Oropharyngeal Cancers: Two Etiologies with Distinct and Shared Mechanisms of Carcinogenesis.

预防口腔癌和口咽癌的综合方法：具有不同和共同致癌机制的两种病因。

DOI：
发表时间：
2020
期刊：
影响因子：
0
作者：
El;Christensen, Neil D;Hu, Jiafen;Viscidi, Raphael;Stairs, Douglas B;Walter, Vonn;Chen, Kun;Sun, Yuan;Muscat, Joshua E;Richie Jr, John P
通讯作者：
Richie Jr, John P

Influence of Tobacco Variety and Curing on Free Radical Production in Cigarette Smoke.

烟草品种和烘烤对卷烟烟雾中自由基产生的影响。