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.

项目总结