) The overall objective of this revised renewal application remains to discover and characterize novel cancer chemopreventive agents derived from the natural products. This Core replaces Project 4 of the renewal application. It will continue to utilize murine mammary gland organ culture (MMOC) assay to evaluate biological effectiveness of potential chemopreventive agents identified in the initial screens of Project 3. As indicated by the theme of this program, extracts or fractions provided by Project 2 and considered as active leads by Project 3 will be first evaluated for chemopreventive activity against 7,12- dimethylbenz(a)anthracene (DMBA)-induced mammary lesions in organ cultures. If the extract shows significant activity in one or both of these systems, bioassay-guided fractionation will be performed (Project 2 and 3). Newly identified agents, which are considered active in Project 3 are again evaluated against mammary lesion formation. In addition to evaluating extracts and pure compounds for their activity against DMBA-induced alveolar lesions, we will also evaluate potential plant extracts and pure compounds with possible anti-estogenic activity (Project 3) for their effect on estrogen-proesterone-dependent DMBA-induced mammary ductal-lesions. In summary, this MMOC Core will serve to provide a secondary discriminatory assay system to select new chemopreventive agents for further evaluation.
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