Interactions between tobacco smoke constituents in rodent tumor models

啮齿动物肿瘤模型中烟草烟雾成分之间的相互作用

• 批准号: 9260881
• 负责人: Lisa A Peterson
• 金额: $ 56.36万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-15 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9260881
• 关键词: A/J Mouse; Acetaldehyde; Acrolein; Aftercare; Aldehydes; Animals; Benzo(a)pyrene; Biological Markers; Biometry; Breathing; Butanones; Carcinogens; Cells; Chemicals; Cigarette; Complex Mixtures; DNA Adducts; Dose; Ensure; Esophageal Neoplasms; Exposure to; Formaldehyde; Formulation; Furans; Goals; Health; Human; Inbred F344 Rats; Incidence; Individual; Injection of therapeutic agent; Link; Lung; Lung Neoplasms; Malignant Neoplasms; Measures; Modeling; Mus; N' -nitrosonornicotine; Nitrosamines; Outcome; Pathway interactions; Phenols; Positioning Attribute; Property; Protocols documentation; Rattus; Research; Residual state; Risk Assessment; Rodent; Safety; Smoke; Tobacco; Tobacco smoke; Tobacco-Associated Carcinogen; Toxic effect; Tumorigenicity; carcinogenicity; design; drinking water; experimental study; exposed human population; genotoxicity; male; public health relevance; repaired; tobacco exposure; toxicant; tumor; tumorigenic; urinary

DESCRIPTION (provided by applicant): Tobacco smoke is a complex mixture of chemicals, many of which are toxic and carcinogenic. How these chemicals interact to cause the human health effects of tobacco smoke and products is not well-understood. To decrease the toxicity and carcinogenicity of tobacco products and smoke, it is important to identify which of the many tobacco constituents to target for reduction. Lowering the levels of one type of chemical may not reduce the overall carcinogenic properties of the tobacco product if interactions amplify the effects of residual levels of the known human carcinogens. Given the complexity of the mixtures and the lack of information regarding how individual components of the mixtures act together to trigger cancer, we will explore the interactions between combinations of two chemicals that are likely to have synergistic tumorigenic effects. The goal of this project is to characterize the potential interactions between known human carcinogens (NNK, NNN, or BaP) and volatile components of tobacco smoke (acetaldehyde, acrolein, and formaldehyde) in established rodent tumor models as outlined in the following specific aims: Aim 1. Determine if acetaldehyde can influence the carcinogenic properties of NNN in a rat esophageal tumor model. Aim 2. Determine if inhaled aldehydes (formaldehyde, acetaldehyde, acrolein) can modulate the carcinogenic properties of NNK in the A/J mouse lung tumor model. Aim 3. Determine if inhaled aldehydes (formaldehyde, acetaldehyde, acrolein) can modulate the carcinogenic properties of BaP in the A/J mouse lung tumor model. In each aim, we will explore the influence of each aldehyde in combination with NNN, NNK, or BaP on tumor incidence, tumor multiplicity and tumor size to determine if reduction of both carcinogen and aldehyde is necessary to reduce harm, or if reductions in one group of constituents would suffice. Urinary metabolite and DNA adduct biomarkers will be measured to determine if the levels of these biomarkers are influenced by the co-exposure. These studies will provide important missing information about the ability of volatile compounds to influence the tumorigenic activity of established tobacco carcinogens

描述（由申请人提供）：烟草烟雾是一种复杂的化学物质混合物，其中许多有毒且致癌。这些化学物质如何相互作用导致烟草烟雾和产品对人类健康产生影响尚不清楚。为了降低烟草制品和烟雾的毒性和致癌性，确定要减少的烟草成分中的哪一种非常重要。如果相互作用放大了已知人类致癌物残留水平的影响，那么降低一种化学物质的水平可能不会降低烟草产品的总体致癌特性。鉴于混合物的复杂性以及缺乏关于混合物的各个成分如何共同作用引发癌症的信息，我们将探索可能具有协同致瘤作用的两种化学物质的组合之间的相互作用。该项目的目标是在已建立的啮齿动物肿瘤模型中表征已知人类致癌物（NNK、NNN 或 BaP）与烟草烟雾挥发性成分（乙醛、丙烯醛和甲醛）之间的潜在相互作用，具体目标如下：目标 1. 确定乙醛是否会影响大鼠食管肿瘤模型中 NNN 的致癌特性。目标 2. 确定吸入的醛类（甲醛、乙醛、丙烯醛）是否可以调节 A/J 小鼠肺肿瘤模型中 NNK 的致癌特性。目标 3. 确定吸入的醛类（甲醛、乙醛、丙烯醛）是否可以调节 A/J 小鼠肺肿瘤模型中 BaP 的致癌特性。在每个目标中，我们将探讨每种醛与 NNN、NNK 或 BaP 组合对肿瘤发生率、肿瘤多样性和肿瘤大小的影响，以确定是否有必要同时减少致癌物和醛来减少危害，或者是否需要减少其中一种物质一组选民就足够了。将测量尿液代谢物和 DNA 加合物生物标志物，以确定这些生物标志物的水平是否受到共同暴露的影响。这些研究将提供有关挥发性化合物影响已确定的烟草致癌物的致瘤活性的能力的重要缺失信息