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.
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