ANALYSIS OF COLD WAR C14 LEVELS IN DNA FROM HUMAN PROSTATE TISSUES

人类前列腺组织 DNA 中冷战时期 C14 水平的分析

• 批准号: 8362767
• 负责人: Donald James Vander Griend
• 金额: $ 11.7万
• 依托单位: UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362767
• 关键词: American; Archives; Benign Prostatic Hypertrophy; Biology; C14 isotope; Carbon; Cell physiology; Cells; DNA; Data; Date of birth; Development; Disease; Etiology; Funding; Generations; Goals; Grant; Growth; Health; Human; Individual; Institution; Life; Longevity; Maintenance; Malignant neoplasm of prostate; Measurement; Measures; Methods; National Center for Research Resources; Patients; Principal Investigator; Prostate; Prostatic; Prostatic Diseases; Quality Control; Reporting; Research; Research Infrastructure; Resource Development; Resources; Source; Specimen; Staging; Stem cells; Testing; Time; Tissue Extracts; Tissues; United States National Institutes of Health; War; accelerator mass spectrometry; anticancer research; cell type; cost; human DNA; male; men

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Introduction: Prostate diseases such as prostate cancer and prostatic enlargement (i.e. benign prostatic hyperplasia, or BPH) are major health problems among American men. The growth of the prostate gland occurs in various stages throughout the lifespan of male individuals, and both prostate cancer and BPH are the result of aberrant cellular turnover and growth. However, this process of cellular turnover is very poorly understood, particularly in humans. The goal of this project is to use AMS to measure Carbon-14 levels in the DNA of prostate cells as a result of Cold War atomic bomb testing. Measurement of Carbon-14 in the post-bomb testing era allows an accurate assessment of tissue turnover and cellular birth-dates; such an approach allows important questions in prostate biology research to be answered regarding the etiology of prostate disease. Methods: DNA will be extracted from tissue specimens, quality controlled, and submitted for Carbon-14 analyses using AMS. Tissue specimens will include archived tissue specimens from our institution (1955  present), as well as fresh prostate tissue specimens from patients currently at our institution. Carbon-14/Carbon-12 ratios will be compared to the known atmospheric Carbon-14 levels, as previously reported, and tissue and cellular "dates of birth" will be determined. Anticipated Results: We anticipate that AMS will accurately determine the rate of turnover within the prostate cellular compartments, and that such Carbon-14 levels will indicate the time of disease development when compared between normal prostate, prostate cancers, and BPH. Furthermore, such an approach will document the average lifespan of the various cell types within the prostate gland, such as the long-lived prostate stem cell. Finally, data generated from these studies will greatly facilitate the generation of new hypotheses regarding prostate function and disease etiology. Impact: Data generated from these studies will have an immediate impact on the field of prostate cancer research and will facilitate answers to essential - and as yet unanswered - questions pertaining to prostate growth, maintenance, and the etiology of prostate disease.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 简介：前列腺癌和前列腺肥大(即良性前列腺增生症，简称BPH)等前列腺癌是美国男性的主要健康问题。在男性的一生中，前列腺的生长发生在不同的阶段，前列腺癌和良性前列腺增生症都是细胞异常周转和生长的结果。然而，人们对细胞周转的这一过程知之甚少，尤其是在人类身上。该项目的目标是使用AMS测量冷战原子弹试验后前列腺细胞DNA中的碳-14水平。在后炸弹测试时代测量碳-14可以准确评估组织周转和细胞出生日期；这种方法可以回答前列腺生物学研究中关于前列腺疾病病因的重要问题。 方法：从组织标本中提取DNA，进行质量控制，并使用AMS进行碳14分析。组织标本将包括来自我们机构的存档组织标本(1955年至今)，以及来自目前在我们机构的患者的新鲜前列腺组织标本。碳-14/碳-12的比率将与已知的大气碳-14水平进行比较，如先前报道的那样，并将确定组织和细胞的“出生日期”。 预期结果：我们预计AMS将准确地确定前列腺细胞间隔内的周转率，当与正常前列腺癌、前列腺癌和BPH进行比较时，这种碳-14水平将指示疾病发展的时间。此外，这种方法将记录前列腺内各种细胞类型的平均寿命，例如长寿的前列腺干细胞。最后，这些研究产生的数据将极大地促进关于前列腺功能和疾病病因的新假说的产生。 影响：这些研究产生的数据将对前列腺癌研究领域产生立竿见影的影响，并将有助于回答有关前列腺生长、维护和前列腺癌病因学的基本问题--这些问题尚未得到回答。