Biology of the Oral Epithelium of E-Cigarette Smokers

电子烟吸烟者口腔上皮的生物学

• 批准号: 9208723
• 负责人: RONALD G CRYSTAL
• 金额: $ 25.43万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-03 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9208723
• 关键词: 21 year old; Acute; Adverse effects; Aerosols; Affect; Age; Attention; Biology; Biopsy; Breathing; Cells; Cellular biology; Chronic; Cigarette; Cigarette Smoker; Clinical; Code; Cohort Studies; Communities; Computational Biology; DNA Methylation; Data; Data Set; Devices; Disease; Electronic cigarette; Electronics; Elements; Epithelial; Epithelium; Ethnic Origin; Future; Gender; Gene Expression; Genes; Glycerol; Health; Host Defense; Human; In Vitro; Ions; Knowledge; Laboratories; Link; Liquid substance; Lithium; Marketing; Messenger RNA; MicroRNAs; Mouth Diseases; Nicotine; Oral; Oral health; Oral mucous membrane structure; Pathway interactions; Pilot Projects; Population; Process; Propylene Glycols; Proteins; Recording of previous events; Respiratory System; Respiratory tract structure; Risk; Smoke; Smoker; Smoking; Smoking History; Suction; TP53 gene; Tobacco; Tobacco smoking; Untranslated RNA; aerosolized; age group; base; carcinogenesis; cigarette smoking; cohort; disorder risk; epigenome; experience; genome-wide; in vivo; insight; never smoker; non-smoker; oral cavity epithelium; propellant; receptor; sensor; transcriptome; vapor; young adult

 DESCRIPTION (provided by applicant): Electronic cigarettes (EC) are battery powered nicotine delivery devices that aerosolize nicotine. Despite the increasing use of EC, little attention has been paid to their possible adverse effects on human health. Theoretically, the risk relates to nicotine per se and/or the propellants or contaminants in the EC aerosol. The hypothesis underlying our application is that chronic EC smoking disorders the biology of the oral epithelium, the first cell population exposed to inhaled EC vapors. There is compelling evidence to support this hypothesis: (1) EC vapors contain nicotine, the oral epithelium expresses nicotine receptors, and exposure of epithelia to nicotine activates the nicotine pathway; (2) EC vapors also contain contaminants that potentially can affect oral epithelial biology; and (3) in vitro studies suggest that EC vapors modify epithelial biology and data generated by our laboratory demonstrates that even a brief, acute exposure of healthy nonsmokers to EC vapors induces significant changes in the airway epithelial transcriptome, including the expression of genes in the nicotine and p53 pathways. Using a cross-sectional, cohort-comparison of EC smokers compared to age, gender and ethnicity-matched never smokers, we propose to assess the oral epithelium obtained by biopsy from 200 EC smokers and 50 nonsmokers. The EC study cohort will be restricted to young adults (age 21-35 yr) with no prior history of tobacco smoking, but who have smoked EC for >6 months. With the knowledge that disordering of cell biology occurs long before clinical disease, we will evaluate the oral epithelium at the epigenome (DNA methylation) and transcriptome (mRNA and miRNA) levels (Specific Aim 1). With the complementary expertise of the co-PIs (R. Crystal, biology of the epithelium, J. Mezey, computational biology), by integrating analysis at the epigenome and transcriptome levels, we will identify gene(s)/pathways/communities disordered by EC vapors (Specific Aim 2). Based on our preliminary data, we will initially focus on the nicotine, p53 and related pathways at the protein and post-translational levels. Because there is so little known about the effects of EC smoking on the oral epithelium, we cannot predict which other biologic processes will be affected, but it is likely that EC vapors influence biology linked to host defens and/or early carcinogenesis. Based on these considerations, we propose 2 Specific Aims. Specific Aim 1: To evaluate the hypothesis that EC smoking alters oral epithelial biology, biopsies will be collected from the buccal mucosa of chronic EC smokers and healthy nonsmoker controls, none of whom have a history of smoking any tobacco products. Genome-wide datasets will be generated to assess DNA methylation and both coding and non-coding RNA transcriptomes. Specific Aim 2: Using both computational and experimental approaches, the biopsies and genome-wide datasets generated in Specific Aim 1 will be assessed to identify genes, pathways and gene communities altered in the oral epithelium of EC smokers, including analyses of two pathways (nicotine, p53) identified in our pilot study.

 描述（应用程序提供）：将尼古丁雾化的电子文明送达设备。尽管EC的使用越来越多，但很少关注他们对人类健康的不利影响。理论上，EC气溶胶中的尼古丁本身和/或推进剂或污染物的风险关系。我们应用的基本假设是，慢性EC吸烟障碍是口服上皮的生物学，这是暴露于掺入EC蒸气的第一个细胞群体。有令人信服的证据可以支持这一假设：（1）EC蒸气含有尼古丁，口服上皮表达尼古丁受体，上皮细胞暴露于尼古丁激活尼古丁途径； （2）EC蒸汽还含有可能影响口服上皮生物学的污染物； （3）体外研究表明，EC蒸汽修改了我们实验室产生的上皮生物学和数据表明，即使是健康的非吸烟者对EC蒸气的短暂，急性暴露也会引起气道上皮转录组的显着变化，包括基因表达的基因表达，在氨基氨酸和p53途径中表达。与年龄，性别和种族匹配的永不吸烟者相比，使用EC吸烟者的横截面，同伴比较，我们建议评估来自200名EC吸烟者和50名非吸烟者的活检获得的口腔上皮。 EC研究队列将仅限于年轻人（21 - 35岁），没有烟草吸烟史，但吸烟ec持续了6个月。知道细胞生物学的无序发生在临床疾病之前很久，我们将评估表观基因组（DNA甲基化）和转录组（mRNA和miRNA）水平（特定目标1）处的口腔上皮。借助Co-Pis的完整专业知识（R. Crystal，上皮生物学，J。Mezey，计算生物学），通过整合表观基因组和转录组水平的分析，我们将确定EC Vapors dise的基因/途径/社区/社区（特定AIM 2）。根据我们的初步数据，我们最初将重点关注蛋白质和翻译后水平的尼古丁，p53和相关途径。 Because there is so little known about the effects of EC smoking on the oral epithelium, we cannot predict which other biologic processes Specific Aim 1: To evaluate the hypothesis that EC smoking alters oral epithelial biology, biopsies will be collected from the buccal mucosa of chronic EC smokers and healthy nonsmoker controls, none of whom have a history of smoking any tobacco products.将生成全基因组数据集以评估DNA甲基化以及编码和非编码RNA转录组。特定目标2：使用计算方法和实验方法，将评估在特定目标1中生成的活检和全基因组数据集，以识别EC吸烟者口服上皮的基因，途径和基因群落，包括对我们的PILOT研究中确定的两种途径（Nicotine，p53）的分析。