Laboratory based Evaluation of Tobacco Harm Reduction

基于实验室的烟草危害减少评估

• 批准号: 8146479
• 负责人: JERRY M RICE
• 金额: $ 13.58万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-02 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8146479
• 关键词: Address; Animal Model; Area; Biological Assay; Breathing; Carcinogen exposure; Carcinogenicity Tests; Carcinogens; Characteristics; Chemicals; Cigarette; Communities; Complement; DNA Adducts; Dose; Evaluation; Exhibits; Experimental Models; Exposure to; Funding; Gap Junctions; Genetically Engineered Mouse; Goals; Harm Reduction; Health; Human; In Vitro; Inbred SENCAR Mice; Individual; Institute of Medicine (U.S.); Label; Laboratories; Light; Marketing; Methodology; Methods; Modeling; Morbidity - disease rate; Mus; NIH Program Announcements; Nicotine; Nicotine Dependence; Performance; Persons; Poison; Population; Process; Property; Public Health; Recording of previous events; Relative (related person); Reporting; Research Personnel; Risk; Risk Assessment; Risk Reduction; Science; Screening procedure; Simulate; Skin; Smoke; Smokeless Tobacco; Smoker; Source; Structure of parenchyma of lung; Supplementation; System; TP53 gene; Testing; Tobacco; Tobacco smoke; Tobacco use; Tumorigenicity; authority; base; cancer risk; cigarette smoking; consumer demand; design; disorder risk; experience; genotoxicity; in vivo; in vivo Model; mortality; new technology; nicotine replacement; novel; potential reduced exposure products; programs; research study; response; tobacco exposure; tool; toxicant; tumor; tumorigenic

DESCRIPTION (provided by applicant): The only proven way to reduce cancer risk in smokers is complete cessation, but many smokers are unable or unwilling to quit. Conceptually, if individuals could reduce their exposure to tobacco smoke toxicants, then their risk of disease could be lessened. This concept is known as harm reduction, and could be achieved through the aid of new strategies and tobacco products that provide an alternate source of nicotine. These are called potential reduced exposure products (PREPs)). There are PREPs that are cigarette-like, but also nicotine replacement therapy and smokeless tobacco are also considered to be PREPs. In the past, various experimental models have been used to evaluate tobacco-associated cancer risk, but none of these models are considered to produce sufficient results by themselves, better screening methods are needed, and currently a panel of models is used in combination. PREPs can be tested similarly, but to date, this has not been evaluated. Because PREPs will be used by individuals with widely differing prior tobacco use histories, the testing paradigms call for a assessing risks with reduced exposures following a background of carcinogen exposure (e.g., a "reversed dose-response relationship"). Whether this can be done successfully also has not been evaluated. This proposal will make use of a panel of conventional and novel testing paradigms that will, and importantly we will incorporate exposures using cigarette smoke condensates that simulate "human like" puffing profiles, and assess the effects of varying nicotine exposure. The goals of this proposal are 1) to develop the tools necessary to provide the objective scientific evidence required to adequately evaluate the ability of PREPs to reduce harm in the laboratory setting, and 2) to use these tools to evaluate existing PREPs and new products as they come to market. Both in vitro and in vivo models will be used in a stepped approach, and both conventional (SENCAR mice) and genetically engineered mice will be tested. The animal models will use skin painting exposures, but DNA adducts in lung tissues also will be assessed. The overall purpose of these experiments is to determine the feasibility of testing different types PREPs using experimental models. The importance of this issue is highlighted by the Program Announcement for PREP studies, and this proposal is responsive to that.

描述（由申请人提供）：在吸烟者中，唯一被证实的降低癌症风险的方法是完全戒烟，但许多吸烟者不能或不愿戒烟。从概念上讲，如果个人能够减少接触烟草烟雾有毒物质，那么他们患病的风险就会降低。这一概念被称为减少危害，可以通过提供替代尼古丁来源的新策略和烟草产品来实现。这些被称为潜在减少暴露产品（PREPs）。有类似香烟的prep，但尼古丁替代疗法和无烟烟草也被认为是prep。过去，人们使用了各种实验模型来评估烟草相关的癌症风险，但这些模型都被认为不能单独产生足够的结果，需要更好的筛选方法，目前是一组模型组合使用。prep也可以进行类似的测试，但到目前为止，尚未对其进行评估。由于prep将被具有广泛不同烟草使用史的个体使用，因此测试范式要求在有致癌物接触背景后减少接触的风险评估（例如，“反向剂量-反应关系”）。这是否能成功也没有评估。该提案将利用一组传统的和新颖的测试范式，重要的是，我们将使用香烟烟雾冷凝物来模拟“类似人类”的雾化情况，并评估不同尼古丁暴露的影响。本提案的目标是1)开发必要的工具，以提供充分评估prep在实验室环境中减少危害的能力所需的客观科学证据，以及2)使用这些工具来评估现有的prep和上市的新产品。体外和体内模型将以分步方法使用，常规（senar小鼠）和基因工程小鼠都将进行测试。动物模型将使用皮肤绘画暴露，但肺组织中的DNA加合物也将进行评估。这些实验的总体目的是确定使用实验模型测试不同类型prep的可行性。PREP研究的项目公告强调了这一问题的重要性，本提案对此作出了回应。