Environmental Exposure and DNA Damage

环境暴露和 DNA 损伤

• 批准号: 7593918
• 负责人: JACK A TAYLOR
• 金额: $ 6.72万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7593918
• 关键词: Animals; Area; Biopsy; Bronchoscopy; Cancer Etiology; Carcinogens; Carcinoma in Situ; Cells; Characteristics; Clinical; Clinical Research; Colon; Colorectal Adenoma; Colorectal Cancer; DNA Damage; Daily; Data Analyses; Detection; Diet; Dietary Component; Dietary Factors; Disease; Early Diagnosis; Endoscopes; Environmental Exposure; Environmental Risk Factor; Exposure to; Fluorescence Bronchoscopy; Gene Mutation; Gene Targeting; Genetic Predisposition to Disease; Genus Cola; Goals; Heterocyclic Amines; High temperature of physical object; Human; In Vitro; Individual; Ingestion; Length; Lesion; Loss of Heterozygosity; Lymphocyte; Malignant Neoplasms; Malignant neoplasm of lung; Measurable; Measures; Meat; Methods; Metric; Molecular; Mutation; Neurologic; Normal tissue morphology; Pan Genus; Pattern; Pilot Projects; Play; Premalignant; Prevention; Prospective Studies; Research; Research Design; Risk; Risk Estimate; Rodent; Role; Techniques; Testing; Time; Tissues; Week; Yogurt; base; bronchial epithelium; cancer risk; chlorophyllin; concept; cooking; cruciferous vegetable; design; environmental agent; feeding; genotoxicity; healthy volunteer; heterocyclic aromatic amines; human study; inhibitor/antagonist; lung imaging; outcome forecast; prevent; prospective; repaired; reproductive; tool; tumor; tumor progression

Fluorescence Bronchoscopy and Molecular Characterization of Abnormal Bronchial Lesions (LIFE Study): We have completed the clinical portion of a prospective study of people at high risk for developing lung cancer that is designed to test whether molecular changes in normal and preneoplastic bronchial epithelium are correlated with exposure or neoplastic progression. We used the Lung Imaging Fluorescent Endoscope (LIFE), a bronchoscopy technique that is a sensitive method for detecting premalignant lesions and carcinoma in situ (CIS) to detect, biopsy, and follow preneneoplastic lesions in a prospective manner over time. Multiple biopsies of each individual lesion were collected over time, allowing us to identify mutational patterns related to exposure and to provide better estimates of lung cancer risk, progression, and prognosis. Data analysis for loss of heterozygosity is continuing. Colon Cell DNA Damage Study: Dietary exposures have been implicated in colorectal cancer risk. Such agents may act to increase risk by causing DNA damage or may decrease risk by protecting against DNA damage. For example, heterocyclic aromatic amines, which are formed in meat that is cooked at high temperature, particularly by pan-frying, induce DNA damage and mutations in vitro, increase tumor formation in rodents, and may increase the risk of colorectal adenomas and cancer in humans. Other dietary components have been identified as inhibitors of heterocyclic amine-induced genotoxicity, including cruciferous vegetables, chlorophyllin, and yogurt. However, the effect of exposure to these compounds in causing or preventing DNA damage has not been directly assessed in colon tissues in humans. Based on the results of previous animal and human studies, we hypothesize that daily exposure in humans to well-done, pan-fried meat in a controlled feeding study will result in measurable increases in DNA damage in colon cells, and that such damage can be inhibited in subjects who consume cruciferous vegetables, chlorophyllin tables, and yogurt along with the well-done meat. As a preliminary step toward investigating these hypotheses, we have completed a pilot study of dietary factors and DNA damage, involving 16 healthy volunteers in a four-week controlled feeding study. Our aims in this pilot study were to determine 1) the magnitude of effects on DNA damage in colon cells and lymphocytes after ingestion of fried meat and these putative inhibitors, and 2) the length of time these diets must be consumed in order for these effects to be detected. Data analysis for this study is continuing.

荧光支气管镜检查和异常支气管病变的分子表征（生命研究）： 我们已经完成了一项前瞻性研究的临床部分，该研究旨在测试正常和肿瘤支气管支气管上皮的分子变化是否与暴露或肿瘤进展相关。 我们使用肺成像荧光内窥镜（LIFE），这是一种支气管镜检查技术，是一种敏感方法，用于检测原位病变和癌（CIS）来检测，活检，并随着时间的推移以前瞻性方式遵循前层状病变。随着时间的流逝，收集了每个单个病变的多次活检，使我们能够确定与暴露有关的突变模式，并更好地估计肺癌风险，进展和预后。 杂合性丧失的数据分析仍在继续。 结肠细胞DNA损伤研究： 饮食暴露与大肠癌风险有关。此类药物可以通过造成DNA损伤来增加风险，或者通过防止DNA损伤来降低风险。例如，在高温下煮熟的肉中形成的杂环芳香胺，尤其是通过泛粉，在体外诱导DNA损伤和突变，增加啮齿动物的肿瘤形成，并可能增加人类结肠直肠腺瘤和癌症的风险。其他饮食成分已被确定为杂环胺诱导的遗传毒性的抑制剂，包括十字花科蔬菜，叶绿素和酸奶。但是，在人类的结肠组织中，未直接评估这些化合物在引起或预防DNA损伤中暴露的影响。 根据先前的动物和人类研究的结果，我们假设在受控喂养研究中，人类每天暴露于人类身上，泛滥的肉会导致结肠细胞中DNA损伤的可测量增加，并且可以抑制这种损害的受试者，这些受试者在消耗十字中的蔬菜，叶绿素tables和Yogurt以及Yogurt以及良好的食物中。作为研究这些假设的初步步骤，我们完成了一项对饮食因素和DNA损害的试点研究，其中涉及16名健康志愿者，进行了为期四周的受控喂养研究。我们在这项试验研究中的目的是确定1）摄入油炸肉和这些假定抑制剂后结肠细胞和淋巴细胞中对DNA损伤的影响的大小，以及2）必须消耗这些饮食的时间，以便检测到这些作用。这项研究的数据分析仍在继续。