EFFECTS ON PROTOZOA 749 



well the marked differences in potency between the tri- and pentavalent 

 arsenicals, and further indicate the LD50/ED50 ratio to be generally higher 

 for the trivalents. In human therapy other factors play a role, since in 

 these mouse experiments only the acute effects and blood clearance were 

 determined. There is some variability in the LD50/ED50 ratio, but not 

 nearly as much as in either dosage, confirming the concept that the toxic 

 and trypanocidal potencies run fairly parallel. It should be noted that effec- 

 tive concentrations of the trivalent arsenicals in the body must be quite 

 low. Of course, different species of trypanosome vary in susceptibility to 

 the arsenicals (Kuhs and Tatum, 1937; Eagle and Doak, 1951). Arsenicals 

 having acidic aliphatic side chains and curing Trypanosoma lewisi infections 

 in rats may be ineffective against Trypanosoma equiperdum, for which 

 derivatives with basic side chains are more effective. 



Effects on Protozoa Other Than Spirochaetes and Trypanosomes 



Most protozoa are not as sensitive to the arsenicals as are the trypano- 

 somes and spirochaetes, as may be seen from the data in Table 6-14, al- 

 though in certain instances the organic arsenoxides are quite potent. There 

 is no reason, of course, for expecting so diversified a group as the protozoa 

 to respond in a manner even remotely uniform; one knows that various 

 types of protozoa have quite different metabolic patterns. Two investigations 

 of the relation of structure to action have been made and the results are 

 presented in Table 6-15. One fact stands out clearly: the high potency of 

 the disubstituted arsenicals, particularly when it is considered that a lethal 

 action within 3 min is the end-point. It is also evident that aromatic de- 

 rivatives are more potent than aliphatic ones. One might imagine that the 

 action is unrelated to the arsenic group, but four pentavalents tested on 

 Colpidium gave relative activities of 6-16, so that, unless permeability to 

 these is low, some specific attack by the diphenyl derivatives appears to 

 be implied. It would be very interesting to know what enzyme and meta- 

 bolic disturbances are produced by these disubstituted arsenicals, and if 

 monothiol enzymes are indeed involved. Further investigation of the actions 

 of these arsenicals on ciliates and other protozoa at lower concentrations 

 and over longer periods of time would be worthwhile, since it might be 

 more important to know the changes when motility is depressed or growth 

 is reduced. The only information we have is the effects of arsenite on Para- 

 mecium: 0.1 mM slows the activity, inhibits acetate utilization 90%, 

 depresses respiration 60%, and increases glucose utilization 15%, all of 

 which fits in with the standard picture of action on keto acid oxidation 

 (Holland and Humphrey, 1953). The motility of Tetrahymena is also re- 

 duced at 0.1 mM arsenite, and this is followed by cytological changes pro- 

 gressing to death; the cytoplasm becomes granular, the macronucleus 

 swells and degenerative spheres appear in it, the nuclear composition is 



