THIS PROPOSAL IS FOR EXTENDING STUDIES RELATED TO THE EVALUATION OF POLYCATION HEXADIMETHRINE (HDM) AND ITS COMPONENTS AS ANTICANCER AGENTS.

THIS PROPOSAL IS FOR EXTENDING STUDIES RELATED TO THE EVALUATION OF POLYCATION HEXADIMETHRINE (HDM) AND ITS COMPONENTS AS ANTICANCER AGENTS. THESE INVESTIGATORS HAVE DEMONSTRATED A DIFFERENTIAL EFFECT OF HDM ON MIXED LYMPHOCYTE CELL CULTURE (MLC) AND ON L1210 CELLS. AT THE DOSES WHICH INHIBIT (3)H-THYMIDINE INCORPORATION INTO L1210 CELLS BY 50 PERCENT, THE RESPONSE OF THE MLC WAS STIMULATED TWO-FOLD. SINCE HDM IS A HETEROGENEOUS MIXTURE OF DIFFERENT MOLECULAR WEIGHTS, THIS PROPOSAL IS FOR ISOLATION OF THE MOST ACTIVE MOLECULAR WEIGHT FRACTION AND ITS EVALUATION BOTH "IN VITRO" AND "IN VIVO", AGAINST L1210 AND P388 LEUKEMIAS AND ON MIXED LYMPHOCYTE CULTURE. RESOLUTION WILL BE ATTAINED BY SEPHADEX GEL FILTRATION CHROMATOGRAPHY AND THE ACTIVE FRACTION(S) WILL BE IDENTIFIEDIN "IN VITRO" CELL CULTURE ASSAYS. SINCE HDM COULD CAUSE MAST CELL DEGRANULATION, SOME OF THE ANTITUMOR EVALUATION STUDIES WILL BE CARRIED OUT IN CONJUNCTION WITH ANTIHISTAMINE THERAPY, ESSENTIALLY INVOLVING TREATMENT WITH BENZALKONIUN CHLORIDE OR DIPHENHYDRAMINE TYPE DRUGS.