The 3PS (mouse leukemia) (P388) in vivo bioassay, currently employed extensively by the National Cancer Institute (NCI) for the detection of antitumor activity, is expensive, relatively complicated, sometimes not reproducible, and time-consuming (often one waits for over two months before receiving results from the NCI contractors). A simple alternative, the crown gall tumor disc bioassay performed on potatoes with a 12 day waiting period, has excellent statistical correlations (p less than 10 to the -6) with 3PS activities in the assay of active plant extracts and active compounds. The proposed research would employ this new antitumor bioassay to guide the phytochemical screening and fractionation of the active principles in 3PS active plant materials. The specific, 3PS active, plant materials to be studied are seeds of five selected species of Euphorbiaceae and sap-extracts of four Costa Rican trees. These materials have already been demonstrated to have significant potato disc/3PS activity. An even faster and simpler assay in brine shrimp will be used in those cases where the antitumor compounds appear to show lethality to the shrimp. These two assays have already been combined in our laboratory both to detect 3PS activity and to isolate the 3PS antileukemic component from the seeds of Euphorbia lagascae. This model project should show convincingly that these very simple and inexpensive bioassays can be used, in house, by natural product chemists to guide the fractionation and isolation of new antitumor agents from plant materials; the future savings of research time and money would be a tremendous boon to the development of new antitumor agents.
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