Mechanism of Chemotherapeutic Action. II. Rôle of Reticuloendothelial System in Formation of a Parasitotropic Agent from Arsenicals.

Recently many investigator 1 - 10 have attempted to study the rôle of the host in chemotherapeutic action by investigating the influence of blockade of the reticulo-endothelial system. They found that different chemotherapeutic agents were less effective with blocked, or blocked and splenectomised animals than with normals. From prior experiments 11 it appears that even as active an agent against trypanosomes as Bayer 205 needs the host's normal protective mechanism for the destruction of the parasites. Thus it was to be expected that blockade would influence unfavorably the course of an infection whether or not a chemotherapeutic agent was also applied. Confirming this view, Kikuth and Regendanz's experiments indicate that treated and non-treated infections are influenced similarly by the blockade. On the other hand, it is known 12 that arsenicals, especially the less diffusible, trivalent compounds are bound and stored in liver and spleen. It was noted especially by Voegtlin, 13 Dyer and Miller that storage favors the chemothera-peutic action. Theories have also been advanced according to which the chemotherapeutic agent stimulates the reticulo-endothelial system 7 or this system inhibits the agent from exerting its action 8 or transforms it into a more active agent. There are no experimental proofs that the influence of the reticulo-endothel is more than what one could expect from its known functions in intermediary metabolism and in detoxification.

Since we 14 have demonstrated that arsenicals are transformed in the host into a more active parasitotropic agent, we thought to obtain some idea of the importance of the reticulo-endothel in chemotherapeutic action by investigating its influence on formation of this active agent in non-infected, arsenical-treated animals.