270 1. lODOACETATE AND lODOACETAMIDE 



Protozoa 



The results reported on ciliates are quite variable. Wertheimer (1932) 

 found the motility of Parameciwm caudatvm to be uninfluenced by bromo- 

 acetate, even in the presence of cyanide, but Calcutt (1950) claimed that 

 0.5 mM iodoacetate kills 90% of the cells of Paramecium hursaria within 

 32 min in the dark and 14 min in the light. The effect of light was believed 

 to be due to its making more SH groups available for reaction. The pH 

 must be important here but in neither work was it given. The motility of 

 Tetrahymena pyriformis is unaffected by 0.03 mM iodoacetate, reduced by 

 0.1 mM, and abolished by 0.3 mM within 60 min, this being apparently 

 at pH 7.3 (Ryley, 1952). It would be interesting to know if there is direct 

 action on the cilia and their contractile elements, but in none of the work 

 can correlations be made. 



Trypanosomes are apparently very sensitive to iodoacetate, so much so 

 that iodoacetate can be used as a chemotherapeutic agent. Smythe and 

 Reiner (1933) first showed that 1 mM iodoacetate kills Trypanosoma equi- 

 perdum within 2-3 min. Injection of tolerated doses of iodoacetate into in- 

 fected rats leads to a clearing of the blood of the organisms in 2-3 hr; the 

 blood remains free of the trypanosomes for several days, and then they 

 reappear. Further doses clear the blood repeatedly but do not eradicate the 

 organisms. Von Jancso and Von Jancso (1936) confirmed these observations 

 for both iodoacetate and bromoacetate, and noted a progressive slowing 

 of motility until the organisms disappear from the blood. T. leuisi motility 

 is abolished by 0.1 mM iodoacetate at a pH of 7.3, respiration being simul- 

 taneously depressed 50% (Ryley, 1951). T. vivax is apparently sensitive 

 to the same degree (Desowitz, 1956). T. rhodesiense is killed by 0.03 mM 

 iodoacetate (Williamson, 1959 b). The facts that trypanosomes are inhib- 

 ited so readily at higher pH's and that iodoacetamide is no more potent 

 than iodoacetate indicate that penetration of the inhibitor is not seriously 

 impeded. Entamoeba histolytica does not survive in 0.04 mM iodoacetate 

 but the associated bacteria are inhibited only some 32% (Yang, 1959). 

 The addition of pyruvate counteracts the depression of the bacterial growth 

 but does not alter the inhibition of the amebae, and because of this it was 

 concluded that a direct action of the iodoacetate on the amebae is likely. 

 Certainly it does not seem to be through an inhibition of the bacteria. 



COMPARISON OF HALOGENATED ACIDS AND 

 THEIR DERIVATIVES 



It is quite possible that for certain purposes iodoacetate is not the ideal 

 alkylating agent, and thus in this section we shall compare iodoacetate with 

 iodoacetamide, with bromoacetate and chloroacetate, and with various 



