Assessing Toxicant Properties and Health Effects of Cigarillo and Hookah Tobacco Aerosols in Rats

评估小雪茄和水烟气溶胶对大鼠的毒性特性和健康影响

• 批准号: 10413991
• 负责人: Steven A Belinsky
• 金额: $ 63.69万
• 依托单位: LOVELACE BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10413991
• 关键词: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; Address; Aerosols; Affect; Age; Air; Aldehydes; Animal Model; Aorta; Aortic Aneurysm; Atmosphere; Benchmarking; Biological Assay; Biological Markers; Biosensor; Bronchoalveolar Lavage; Carboxyhemoglobin; Carcinogens; Cardiac; Cardiopulmonary; Cardiovascular system; Cell Count; Cells; Charcoal; Chronic Obstructive Pulmonary Disease; Cigar Smoking; Cigarette; Collection; Complex; Contracts; Coronary heart disease; Cotinine; Coupled; DNA Adducts; DNA strand break; Data; Development; Disease; Dose; Endothelium; Epithelial Cells; Exposure to; Freezing; Funding; Gases; Gene Expression; Generations; Genes; Hazardous Chemicals; Health; Heart; Histopathology; Immune; In Vitro; Inflammation; Inflammatory; Inhalation; Inhalation Exposure; Intercellular adhesion molecule 1; Interleukin-12; Interleukin-6; Link; Lipid Peroxidation; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Measurement; Mission; Molecular; Nicotine; Nitrosamines; Nose; Oral; Outcome; Oxidative Stress; Oxygen; Particulate; Particulate Matter; Pathway interactions; Physiological; Plasma; Plethysmography; Policies; Property; Protocols documentation; Pulmonary Heart Disease; Pulmonary Inflammation; Rattus; Reactive Oxygen Species; Reporting; Research; Risk; Science; Serotonin; Serum; Smoke; Smoking; Standardization; System; Tars; Testing; Thiobarbituric Acid Reactive Substances; Thoracic aorta; Tissues; Tobacco; Tobacco smoke; Toxic effect; Work; abdominal aorta; base; cardiovascular effects; cardiovascular health; chemical property; cigarette smoking; cigarillos; combustible tobacco; cytokine; cytotoxic; cytotoxicity; design; epidemiology study; evidence base; experience; genome-wide; genotoxicity; hookah; immunoregulation; in vivo; innovation; lung development; neutrophil; particle; physical property; predictive tools; pulmonary function; respiratory; response; sex; smoke inhalation; tobacco exposure; tobacco products; tobacco regulatory science; toxicant; transcriptional reprogramming; young adult

Project Summary Nearly 16% of US young adults ages 18–24 report smoking cigars and a recent review documents growing evidence linking this product to lung cancer, coronary heart disease, aortic aneurysm and COPD. Similarly, epidemiological studies link waterpipe tobacco to these same diseases. To date, there are few studies characterizing health effects of these tobacco aerosols in animal models. The specific aims and research strategy derive from these research gaps and address two of the scientific domains in the RFA, toxicity and health effects. As mandated by the FDA, the studies are not mechanistic, but are designed to compare responses and effects across tobacco products (cigarettes, cigarillos, and hookah). The central hypothesis of this application is that cigarillo and hookah tobacco products will show significantly greater differences across one or more of the five health outcomes (cancer, transcriptional reprogramming, lung function and inflammation, cardiovascular effects and serum circulatory inflammation) being studied when compared to cigarettes. Building on more than two decades of experience in characterizing the physical and chemical properties of complex aerosols, aim 1 will use a recently developed 14-day rat nose only exposure system to provide comprehensive dose response characterization of hazardous chemicals in the exposure atmosphere linked to cancer and cardiopulmonary diseases between cigarettes, cigarillos, and hookah products. Quantitation of carboxyhemoglobin levels in response to increasing dose of the tobacco aerosols will be correlated with cardiovascular health effects biomarkers assessed under Aim 2, while plethysmography will evaluate exposure effects on pulmonary function. Aim 2 will use biospecimens collected following the 14-day exposures to assess effects across the five health outcomes described above. Sensitive and quantitative readouts of these cardiopulmonary biomarkers will be obtained to enable comparisons across products and to evaluate the effect of dose for informing differences in potency. A comprehensive set of biomarkers has been selected to enable identification of the most sensitive readouts for predicting long-term health effects. These biomarkers include specific DNA adducts, lipid peroxidation, cytokine panels, global assessment of lung transcriptional reprogramming, specific gene expression changes in heart and aorta and expression changes predictive for circulatory inflammation. Findings from these studies will support the establishment of new evidence-based regulatory policies for these products that in turn, will inform the public of their hazardous properties.

项目概要 近 16% 18-24 岁的美国年轻人表示吸雪茄，最近的一份审查文件 越来越多的证据表明该产品与肺癌、冠心病、主动脉瘤和慢性阻塞性肺病有关。 同样，迄今为止，很少有流行病学研究将水烟与这些疾病联系起来。 研究表征这些烟草气溶胶对动物模型的健康影响的具体目标和。 研究策略源于这些研究差距，并解决 RFA 中的两个科学领域， 根据 FDA 的规定，这些研究不是机械性的，而是旨在 比较不同烟草产品（香烟、小雪茄和水烟）的反应和效果。 该应用的假设是小雪茄和水烟烟草产品将表现出明显更大的 五种健康结果（癌症、转录重编程、肺癌）中一项或多项的差异 功能和炎症、心血管影响和血清循环炎症）正在研究中 与香烟相比，建立在二十多年的物理和表征经验的基础上。 复杂气溶胶的化学特性，目标 1 将使用最近开发的 14 天仅大鼠鼻子暴露 系统提供暴露中危险化学品的全面剂量反应特征 香烟、小雪茄和水烟之间的气氛与癌症和心肺疾病有关 随着烟草气溶胶剂量的增加，对碳氧血红蛋白水平进行定量。 与目标 2 下评估的心血管健康影响生物标志物相关，而体积描记法将 目标 2 将使用 14 天后收集的生物样本来评估暴露对肺功能的影响。 暴露以评估上述五种健康结果的影响。 将获得这些心肺生物标志物的读数，以便能够进行产品之间的比较并 评估剂量的影响以了解效力的差异已经建立了一套全面的生物标志物。 选择能够识别最敏感的读数来预测长期健康影响。 生物标志物包括特定 DNA 加合物、脂质过氧化、细胞因子组、肺的整体评估 转录重编程、心脏和主动脉的特定基因表达变化以及表达变化 这些研究的结果将支持建立新的循环炎症。 针对这些产品的基于证据的监管政策反过来将告知公众其危险性 特性。