Carcinogenesis cellular model for identifying preventive agents

用于识别预防剂的致癌细胞模型

• 批准号: 7382709
• 负责人: Hwa-Chain Robert Wang
• 金额: $ 7.35万
• 依托单位: UNIVERSITY OF TENNESSEE KNOXVILLE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-27 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7382709
• 关键词: 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone; Address; Benzo(a)pyrene; Biological; Biological Markers; Breast; Cancerous; Carcinogen exposure; Carcinogens; Cell Line; Cell model; Cells; Chronic; Collecting Cell; Dependence; Development; Diet; Disease; Dose; Effectiveness; End Point; Environmental Carcinogens; Environmental Pollution; Epithelial; Epithelial Cells; Exposure to; Foundations; Gene Chips; Gene Expression; Gene Expression Regulation; Genes; Goals; Growth Factor; Health; Healthcare; Human; Individual; Knowledge; MCF10A cells; Malignant Neoplasms; Metabolic; Methods; Molecular; Molecular Profiling; Play; Positioning Attribute; Premalignant; Prevention; Preventive; Property; Reagent; Recipe; Research; Risk; Role; Smoker; Societies; Staging; System; Technology; Testing; Tobacco; Work; cancer prevention; cancer risk; carcinogenesis; cell growth; chemical carcinogen; chemical carcinogenesis; cost; cytotoxic; dietary constituent; dietary supplements; experience; exposed human population; fruits and vegetables; malignant breast neoplasm; metaplastic cell transformation; prevent; success; tobacco exposure

DESCRIPTION (provided by applicant): The ultimate goal of this project is to further develop an efficient cellular model and methods to identify dietary agents for preventing human cancers induced by tobacco and environmental carcinogens. Studies have suggested that exposures to tobacco and environmental carcinogens increase the risk of cancer development in humans. Growing evidence suggests vegetables and fruits can play a protective role in human healthcare by preventing cancers and other diseases. However, there is a serious gap in our understanding of how dietary constituents prevent human cancers associated with chemical carcinogens. The rationale for this project is to establish a low-cost cellular model and methods to study cellular and molecular mechanisms for dietary agents in the prevention of cellular carcinogenesis induced by tobacco and environmental carcinogens. Using cell technology, we have been developing a carcinogenesis-cellular model mimicking chronic exposures of human breast epithelial cells to low doses (levels detected in smokers) of carcinogens. We have been able to induce cells to progressively acquire cancerous properties, from an immortalized non-cancerous stage through identifiable precancerous sub-stages to a cancerous stage. With gene chip technology, our cellular model serves as a system to reveal the molecular markers of carcinogens in the progressive transformation of human epithelial cells. The central hypothesis is that the identifiable, acquired cancerous properties and molecular markers of cellular carcinogenesis are able to serve as biological and molecular endpoints for the prevention of breast cell carcinogenesis, which will then allow us to determine biological and molecular activities of preventive agents for protecting human cells from carcinogenesis. To test this hypothesis, we will address the capability of our carcinogenesis-cellular model to reveal the ability, the mode of action, and the molecular markers associated with dietary suppression of cell acquisition of cancerous properties induced by individual carcinogens. Success of this study will empirically validate our approach of identifying preventive agents to block carcinogenesis associated with tobacco and environmental pollution, and create a foundation for studying the molecular mechanisms involved in the dietary prevention of carcinogen-related cancers. The broad impact is expected to benefit the whole of society by providing an efficient cellular model to identify dietary constituents for formulating diets or supplements that can prevent human cancers related to tobacco exposure and environmental pollution.

描述（由申请人提供）： 该项目的最终目标是进一步开发有效的细胞模型和方法来识别饮食制剂，以预防烟草和环境致癌物诱发的人类癌症。研究表明，接触烟草和环境致癌物会增加人类患癌症的风险。越来越多的证据表明蔬菜和水果可以通过预防癌症和其他疾病在人类保健中发挥保护作用。然而，我们对饮食成分如何预防与化学致癌物相关的人类癌症的理解存在严重差距。该项目的基本原理是建立一个低成本的细胞模型和方法，以研究膳食制剂预防烟草和环境致癌物诱导的细胞癌变的细胞和分子机制。利用细胞技术，我们一直在开发一种致癌细胞模型，模拟人类乳腺上皮细胞长期暴露于低剂量（在吸烟者中检测到的水平）致癌物。我们已经能够诱导细胞逐渐获得癌特性，从永生化的非癌阶段到可识别的癌前亚阶段再到癌阶段。通过基因芯片技术，我们的细胞模型作为一个系统来揭示人类上皮细胞渐进转化过程中致癌物的分子标记。中心假设是，可识别的、获得性的癌特性和细胞癌变的分子标记能够作为预防乳腺细胞癌变的生物学和分子终点，这将使我们能够确定预防剂的生物学和分子活性，以保护乳腺细胞癌变。人体细胞免于致癌作用。为了检验这一假设，我们将讨论我们的致癌细胞模型的能力，以揭示与饮食抑制个体致癌物诱导的细胞获得癌性特性相关的能力、作用模式和分子标记。这项研究的成功将从经验上验证我们确定预防剂来阻止与烟草和环境污染相关的致癌作用的方法，并为研究致癌物相关癌症的饮食预防分子机制奠定基础。通过提供有效的细胞模型来识别膳食成分，以制定可以预防与烟草接触和环境污染相关的人类癌症的饮食或补充剂，预计这一广泛影响将使整个社会受益。