92 ENZYMES AND DRUG ACTION 



been the subject of the most consistent attack, both by 

 enzymologists and by others. In the first instance we 

 must distinguish between the local vesicant effect and the 

 systemic effect of these substances. A survey of the liter- 

 ature shows that there is no common agreement between 

 different workers as to the mode of action of these two 

 substances. Peters is of the opinion that the primary 

 effect of mustard gas is upon the surfaces of skin cells, 

 and possible upon the enzymes in those surfaces. The 

 result of this action is the liberation of proteases which 

 among other effects produce leucotaxin. On the other 

 hand Peters considers that the primary effect of lewisite 

 is upon pyruvic oxidase. 



Dixon and Needham, on the other hand, tend to the 

 view that both substances exercise their primary effect, 

 in common with other vesicants, upon hexokinase and 

 perhaps other phosphokinases. 



American workers in this field have reached somewhat 

 different conclusions, in which they have been influenced 

 by their observation that some proteases are as sensitive 

 to these substances as are the phosphokinases. Cori and 

 Cannan appear to favour the view that the primary 

 effect of mustard gas is upon the cell surface, and results 

 in liberation of enzymes and changes in permeability. 

 A recent American review concludes that "the specific 

 chemical lesion is not yet defined by studies on inacti- 

 vation of enzymes." 



The effect of vesicants on the skin is so dramatic that 



