Differential susceptibility and cytopathic alterations induced by PTT. 119, a new cancericidal compound, p-fluoro-Phe-L-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met ethoxy HCl.
PTT.119 is a new synthetic compound under assessment as a chemotherapeutic agent against neoplasia. Exposure of three diverse tumor cell lines, L1210 leukemia, MJY-alpha mammary tumor, and B16 melanoma to 1 to 50 micrograms PTT.119/ml for 15, 30 or 60 minutes significantly reduced cell survivals. Each tumor model was differentially susceptible to PTT.119 activity in the extent and kinetics of cell cytolysis. Pathological changes unique to each tumor cell type were also observed and included nuclear fragmentation and lobulation, formation of multinucleated cells, mitotic asynchrony and vacuolization of both nuclear and cytosol compartments. The data demonstrate the necessity of using more than one tumor system for the evaluation of compounds and suggest that PTT.119 exerted its cancericidal activity by more than one mechanism.
D000477:Alkylating Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D007939:Leukemia L1210 / Q000188:drug therapy; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; C038259:ambamustine