The anti-tumor action of lysergic acid derivatives and their serotonin-blocking effect as reflected by the I 131 distribution in rats.

Extensive degranulation and fragmentation of the mesenteric mast cells resulting from a subcutaneous rat sarcoma or its polypeptide have been reported previously (7). Subsequent release of histamine and 5-hydroxytryptamine (serotonin or 5-HT) from these cells interferes with distribution of electrolytes in the body, as illustrated by tracer studies with I m (4), Na ~, and BrS~. 1 Studies showed a low excretion of I lal in tumorbearing rats and high uptakes in gastrointestinal tract, skin, and remains which were primarily muscle. This phenomenon, "iodide trapping," has also been observed in rats given tumor polypeptide, histamine, and 5-HT, or subjected to destruction or depletion of mast cells by distilled water, reserpine, or compound 48/80 (1, 4). The relationship of histamine and 5-HT of the mast cell with growth and survival of tumor implants has been established in one rat sarcoma (7). Mast cell depletion prior to tumor implantation reduced the survival. On the other hand, survival and growth increased if mast cells were depleted during tumor growth or if histamine and/or 5-HT was administered. Histamine combined with 5-HT stimulated tumor growth more effectively than did 5-HT alone. The stimulating action of 5-HT on tumor implant survival leads to consideration of the effect of agents which block 5-HT upon tumor cells. A series of blocking agents derived from lysergic acid has been investigated extensively by Gaddum (~), Cerletti and Doepfner (1), and Taeschler and Cerletti (9). The present study, with 1181, concerns the effect of lysergic acid derivatives upon the survival of tumor cells and the efficacy of these 5-HT-blocking agents in the intact rat.