CHEMOTHERAPY 



electron microscopy, much has been done with stains and fixatives, 

 and we are able to assign generic names like protein, fat, carbohydrate, 

 and nucleoprotein to some cell structures. But enzymes, coenzymes, 

 metabolites, antigens, toxins, and such constituents of molecular size 

 are recognized by functional, rather than visual, attributes. Where 

 any means of identifying one of them in the anatomy of the cell is 

 available, it is likely to be an indirect method subject to the same 

 question and criticism as were the methods of early organic chemical 

 science. A few specific constituents of functional interest, like desoxy- 

 ribosenucleic acid, ribosenucleic acid, phosphatase, glycogen, cellulose, 

 heparin, etc., can now be recognized by staining methods when they 

 are localized in large amounts in some structure of the cell. Never- 

 theless, we seldom know both the function, in chemical terms, and the 

 site, of any cell constituent. And even when we do know the chemical 

 potentialities of some unseen constituent, we rarely are able to say 

 when in the life of the cell it is acting and when its activity is latent. 



For information about the cell we can look to the stains, fixa- 

 tives, antiseptics, hypnotics, anesthetics, insecticides, hormones, meta- 

 bolic poisons, growth factors, etc. In short, we will eventually draw 

 upon every situation in which a substance of known constitution pro- 

 duces observable modifications in cells or cell activities. It is quite 

 natural that cytochemical reagents should all be, in varying degrees, 

 toxic substances. Before they can claim interest as therapeutic agents, 

 however, they must prove to be of less than general toxicity, and 

 capable of administration in a form not too easily hydrolyzed, de- 

 stroyed, diff'used away, precipitated out, excreted, or otherwise re- 

 moved from the site of activity in the body. The pharmacist and 

 pharmacologist have become so skilled in controlling and modifying 

 these last aspects of drug action that, in a sense, we shall be justified 

 in concentrating our attention upon the first-mentioned factor, cyto- 

 chemical specificity. 



Ideally, chemotherapeutic agents should have maximal eff'ects 

 upon a chosen variety of cells (a parasitic foreign agent, or a diseased, 

 neoplastic, hyperactive, or otherwise abnormal host tissue) and a 

 minimal eff"ect upon other tissue cells of the organism. For this to 

 be possible it is necessary to capitalize upon structural difi'ercnces 

 between the cells at one of three levels of organization, the morpho- 

 logical, the colloidal, or the chemical level. This is now necessarily 



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