The objective of this study is to examine a variety of potential biomarkers employing the MNU-induced rat mammary and OH BBN-induced mouse bladder tumor models which are routinely employed. The specific endpoints to be employed include: A) Alterations of levels of cell proliferation related endpoints e.g. PCNA and S phase labeling with BudR B) Alterations in apoptosis employing either DNA related assays (Fragmentation or Tunnel) and histopathologic determination of apoptosis C) Cellular Necrosis as determined histopathologically D) use of to FACS analysis to determine aneuploidy, apoptosis and or proliferation. Three sources of tissue in which the multiple biomarker assay are being examined to look for the effects of various chemopreventives: 1) """"""""Normal""""""""Tissue employing RNA, FACS analysis and Western blotting endpoints in addition to any immunohistochemical staining. 2. Preinvasive Lesions such as of lesions in human prevention trials (PIN in prostate; DCIS in mammary; adenomatous polyps in colon, etc.). The primary objective of the present study is to demonstrate modulation of biomarkers in palpable mammary lesions within 4-10 days following initiation of treatment with certain chemopreventives (tamoxifen, vorozole, ) . Four compounds and five doses with agents which exhibit striking chemopreventive efficacy as well as single doses from four compounds which are ineffective as chemopreventives in this specific tumor model.
|Christov, K (2009) To kill tumor cells or permanently paralyze them in senescence? J BUON 14:189-96|