National Cancer Institute, Research Contracts Branch, PCCS, Executive Plaza South, Room 635, Bethesda, Md 20892

A -- EVALUATION OF CHEMOPREVENTIVE AGENTS BY IN VITRO TECHNIQUES SOL MAA-N01-CN-75029-63 DUE 051697 POC Tina M. Huyck, Contracting Officer, 301-435-3830 E-MAIL: Tina M. Huyck, huyckt@rcb.nci.nih.gov. The National Cancer Institute, Division of Cancer Prevention and Control (DCPC), Chemoprevention Branch, wishes to award Master Agreement Contracts for the above study. The required services will be defined by Master Agreement Orders issued during the period of performance. Pursuant to the Master Agreement Orders issued during the period of performance. Pursuant to the Master Agreement Orders (MAOs) the contractor shall screen and evaluate the activity of chemopreventive agents in various in vitro assays relating to the inhibition of cell transformation. Agents with potential chemopreventive activity are identified by epidemiologic surveys, initial laboratory (experimental) findings, observations in the clinical setting, or structural homology with agents having known chemopreventive activity. A rigorous and systematic evaluation of these candidate agents is necessary before their efficacy can be examined in clinical trials for cancer prevention. In vitro screening and evaluation techniques measuring the ability of these chemopreventive agents to inhibit transformation provides a relatively rapid and efficient means of qualifying these agents for further evaluation for the prevention of cancer in humans. Recent progress in the in vitro systems has led to the development of cell culture models and techniques which make possible an evaluation of the effects of various substances on cell transformation. These systems shall allow an evaluation of the efficacy of chemopreventive agents against a variety of initiating and/or promoting substances. The end points measured in the routine assays are either direct transformation (e.g., anchorage independent growth, foci of morphologically altered cells, tumor formation in nude mice) or parameters highly correlated with transformation (e.g., production of messenger RNA encoded by oncogenes, measurement of transforming proteins, clonogenicity of cells). Defined reagents available might include: 1) cell lines of epithelial origin which can be transformed by complete carcinogens or transformed by subcarcinogenic doses of complete carcinogens or incomplete carcinogens. 2) primary cell or organ cultures of epithelial origin which can be transformed. 3) Cloned cells transformed various defined oncogenes and expressing specific transcribed messenger RNA and translated proteins which can be examined for modulation by chemopreventive agents. The transformed phenotype of such cells can be observed directly and is correlated with the levels of these substances which are measured respectively by labeled DNA probes and specific immunologic reagents, 4) Cell lines having defined quantities of epidermal growth factor and tumor growth receptors are useful substrates for evaluating analogues which might block, inhibit or compete with the growth factors. These four systems shall serve as examples or models, other in vitro systems of transformation exist and offerors shall be encouraged to propose these and other in vitro systems which they consider relevant to accomplish the proposed objectives. The potential chemopreventive agents which can be examined by these techniques range from all of the retinoid compounds, antioxidants, growth factor analogs, inhibitors of promotion, antibodies to promoters, to synthetic viral polypeptide vaccines. The use of the in vitro screening system for preventive agents shall serve to: (1) improve the criteria for the selection of chemicals which shall be tested later for efficacy and toxicology in whole animal systems and for assigning priorities to chemicals for further studies, (2) improve the breadth of data on the inhibiting potential of the chemical, (3) evaluate the effect on actual target sites in one or more in vitro systems, (4) decrease later toxicology testing costs by reducing the number of inappropriate compounds reaching that stage in the screening sequence, (5) accelerate the rate at which chemicals are evaluated. If the MAO contractor does not have the equipment, facilities, expertise to carry out a particular portion of a workstatement, they may elect to subcontract portions of the workstatement to insure the optimal performance of the task. The purpose of this acquisition is to qualify contractors to a pool of Master Agreement Holders. The period of performance of the Master Agreement pool will be for five (5) years. It is estimated that up to four (4) Master Agreement Orders per year will be issued pursuant to the Master Agreement contracts. The Master Agreement Announcement will be available on approximately April 7, 1997. The proposal due date will be approximately May 16, 1997. Requests for this solicitation must reference MAA-N01-CN-75029-63. Requests should be E-mailed to Tina M. Huyck at huyckt@rcb.nci.nih.gov. If E-mail is unavailable, please fax your requests to Ms. Huyck at 301-402-8579 or mail to Ms. Tina M. Huyck, Contracting Officer, National Institutes of Health, National Cancer Institute, Research Contracts Branch, PCCS, Executive Plaza South, Room 635, 6120 Executive Boulevard MSC 7226, Bethesda, Maryland 20892-7226. (0083)

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