Western diet as a modifier of benzo(a)pyrene-induced colon carcinogenesis

西方饮食作为苯并（a）芘诱导的结肠癌的调节剂

• 批准号: 8721053
• 负责人: Kelly L Harris
• 金额: $ 4.27万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8721053
• 关键词: Adipose tissue; Adolescent; Adult; Affect; Aldehydes; Animal Model; Animals; Area; Aromatic Polycyclic Hydrocarbons; Benzo(a)pyrene; Biological Assay; Blood; C-reactive protein; CYP1A1 gene; Cancer Etiology; Carcinogens; Carcinoma; Cessation of life; Colon; Colon Carcinoma; Colonic Neoplasms; Colorectal Cancer; Colorectal Polyp; Consumption; DNA; DNA Adducts; DNA Damage; Detoxification Process; Development; Development Plans; Diet; Diet Habits; Dinoprost; Drug Metabolic Detoxication; Energy Intake; Environment; Environmental Risk Factor; Enzymes; Epidemiologic Studies; Epidemiology; Equilibrium; Etiology; Evaluation; Event; Exposure to; F2-Isoprostanes; Family; Fatty acid glycerol esters; Fellowship; Food; Glutathione S-Transferase; Goals; Harvest; Health; High temperature of physical object; Human; Individual; Inflammation; Inflammatory; Interleukin-6; Intervention; Journals; Label; Length; Lesion; Link; Liver; Malignant Neoplasms; Measures; Meat; Mentors; Metabolic; Metabolic Activation; Metabolic Biotransformation; Modeling; Obesity; Oral; Oxidative Stress; Pathway interactions; Peer Review; Play; Polyps; Predisposition; Production; Protein C; Publishing; Rattus; Research; Research Activity; Resources; Risk; Risk Factors; Role; Scientist; Signal Pathway; Source; Testing; Thin Layer Chromatography; Time; Tissues; Toxic Environmental Substances; Training; Transgenic Organisms; Tumor Necrosis Factor-alpha; United States; Unsaturated Fats; Visit; Weight Gain; adduct; adenoma; benzo(a)pyrene-DNA adduct; career development; colon carcinogenesis; cooking; cytokine; environmental chemical; enzyme activity; fast food; feeding; food consumption; forging; fruits and vegetables; genetic regulatory protein; high risk; insight; interest; male; meetings; member; mortality; oxidative DNA damage; polyposis; pre-doctoral; public health relevance; red meat consumption; research study; saturated fat; toxicant; tumorigenesis

PROJECT SUMMARY Benzo(a)pyrene [B(a)P], an ubiquitous environmental toxicant, is a member of the polycyclic aromatic hydrocarbon (PAH) family of compounds and has been implicated in the causation of colorectal cancer (CRC). Additionally, consumption of red meat and saturated fats, toxicants such as PAHs has also been implicated as one of the risk factors for sporadic colon cancer. Our preliminary studies not only show that B(a)P causes colon cancer, but that administration of Western diet to B(a)P-treated Polyposis in Rat Coli (PIRC) rats increases the development of adenomas in the colon. Our proposed studies will test the hypothesis that Western diet exacerbates B(a)P-initiated colon carcinogenesis through altered biotransformation and DNA damage. We will test our hypothesis in adult male transgenic PIRC rats with the following specific aims: 1. Characterize and validate the PIRC rat as a model to study how Western diet potentiates B(a)P-induced colon carcinogenesis; 2. Determine diet-induced alteration of B(a)P biotransformation enzyme activities, expression, and metabolite disposition in the PIRC rat; and 3. Assess the contribution of regular and Western diet in the formation and persistence of B(a)P-DNA adducts and oxidative DNA damage in the PIRC rat. This project will provide new and interesting information with regard to the contribution of Western diet towards increasing the development of colorectal polyps. The goals of this application are also to provide the intellectual environment and resources for the applicant to enrich herself in various approaches in her chosen area of research via a training plan that incorporates: 1) Mentored research activity; 2) Active participation & presentation in meetings, seminars and journal clubs; 3) Interaction with visiting scientists; 4) Periodic evaluation of applicant's research progress through individual development plan; 5) Publishing research findings in peer-reviewed journals; and 6) Participation in career development activities. It is expected that by the end of the training period, the applicant will be successful in her chosen research endeavor and contribute to the diversity of the research workforce, a goal of the Ruth L. Kirschstein predoctoral fellowship. Relevance of this project to human health Colorectal cancer contributes to significant mortalities in the United States, with 50,000 deaths per year. Consumption of fatty foods contaminated with B(a)P was implicated as a causative factor. One-third of adults and 17% of adolescents in the United State are obese. Obese people have a higher risk for colon cancer due to the excess energy intake from Western diet. We plan to study the progression of CRC, using a rat model that mirrors the human CRC scenario. We also propose to use Western diet, (>58% fat), as an accelerator of CRC. Our findings will be of use to determining the mechanistic effects of diet on B(a)P-caused initiation, promotion and progression of CRC.

项目摘要 苯并（a）pyrene [b（a）p]，一种无处不在的环境有毒物质，是多环芳烃的成员 化合物的碳氢化合物（PAH）家族与结直肠癌（CRC）有关。 此外，消耗红肉和饱和脂肪，诸如PAH等有毒物质也被认为是 零星结肠癌的危险因素之一。我们的初步研究不仅表明b（a）p会导致 结肠癌，但在大鼠大鼠（PIRC）大鼠中给予西方饮食对B（A）P（A）P（A） 增加结肠中腺瘤的发展。我们提出的研究将检验以下假设 西方饮食通过改变生物转化和DNA来加剧b（a）p发出的结肠癌发生 损害。我们将在成年男性转基因PIRC大鼠中测试我们的假设，其特定目的是：1。 表征和验证PIRC大鼠是研究西方饮食如何增强B（a）P诱导结肠的模型 癌变； 2。确定饮食诱导的B（a）P生物转化酶活性，表达，， 和PIRC大鼠中的代谢物处置；和3。评估常规饮食和西方饮食在 B（A）P-DNA加合物的形成和持久性和PIRC大鼠中的氧化DNA损伤。这个项目将 提供有关西方饮食对增加的贡献的新有趣的信息 结直肠息肉的发展。该应用程序的目标也是提供智力环境 和申请人的资源，以通过A的研究领域中的各种方法丰富自己 合并的培训计划：1）指导研究活动； 2）积极参与和演示 会议，研讨会和期刊俱乐部； 3）与来访科学家的互动； 4）定期评估申请人的 通过个人发展计划进行研究进展； 5）在同行评审中发布研究结果 期刊； 6）参与职业发展活动。预计到培训结束 时期，申请人将在她选择的研究努力中取得成功，并为多样性做出贡献 研究工作人员，露丝·柯希斯坦（Ruth L. Kirschstein）奖学金奖学金的目标。 该项目与人类健康的相关性 结直肠癌在美国有效死亡，每年50,000例死亡。 B（a）P污染的脂肪食品的消费涉及是一种致病因素。成年人的三分之一 美国有17％的青少年肥胖。肥胖者患结肠癌的风险更高 从西方饮食中摄入过多的能量。我们计划使用大鼠模型研究CRC的进展 这反映了人类CRC场景。我们还建议使用西方饮食（> 58％脂肪）作为加速器 CRC。我们的发现将用于确定饮食对B（a）P引起的启动的机械作用， CRC的促进和进展。