Is Schnitzer's “Interference” Between the Action of Two Chemotherapeutic Substances Due to Surface Reactions?

Abstract

Browning and Gulbransen 1 discovered the remarkable fact that although the injection of basic fuchsin cured rats infected with trypanosomiasis and acriflavine injections had the same effect, if animals previously fed basic fuchsin by mouth were infected with fuchsin-fast trypanosomes, and later acriflavine was injected, the therapeutic action of the acriflavine was prevented and the animals died of trypanosomiasis. They gave to this action the name of “interference phenomenon.” These observations were confirmed by Schnitzer 2 (both with fuchsin-fast and normal trypanosomes) who showed that it applied also to other triphenyl methane dyes, e. g., methyl violet and brilliant green, and to arsenicals, e. g., arsphenamine and arsacetin.

Since these experiments seem to raise questions that are fundamental in the problem of chemotherapy, it is important to determine whether they can be explained as merely surface reactions upon the trypanosomes or whether one must have recourse to other more abstruse processes of metabolism or vital phenomena.

We have therefore attempted to determine whether a similar interference could be demonstrated upon the growth and CO₂ production by yeast in the test-tube. Our curves of CO₂ production by ordinary baker's yeast grown in a sucrose solution show that yeasts which have been definitely stained by methyl violet or by brilliant green in the test-tube, in solutions too weak to affect the CO₂ production, are less sensitive to acriflavine than are normal yeast cells. Vice versa, yeast cells stained with acriflavine in concentration too low to affect CO₂ production, are rendered less sensitive to methyl violet and brilliant green. This effect is not noticeable with basic fuchsin.

These experiments represent a complete parallelism in vitro to Browning's and Schnitzer's “interference phenomenon” in vivo, and render it probable that the latter can be explained as a simple surface reaction.