auerbach: effects of chemicals 121 



substances which make it mutate, we tend to interpret the action of 

 mutagenic compounds on the basis of what we know about the nature 

 of the genetic material. In some cases, notably in mutation experi- 

 ments on virus and bacteriophage, this approach has already given 

 highly interesting results, but as a general attitude to mutation 

 research it narrows the area of investigation and is likely to result in 

 misleading interpretations. Even if we accept it as highly probable 

 that, in higher organisms as well as in bacteria and bacteriophages, 

 the essential genetic specificity resides in the DNA of the chromo- 

 somes, it still remains naive to imagine that a chemical — and often a 

 highly reactive one — introduced into a cell will react with the DNA 

 without at the same time producing a variety of chemical changes in 

 the remaining constituents of the cell. Mutation, as we now know, 

 is a complicated process of which we usually only see the beginning 

 and the end: the introduction into the cell of a mutagenic a^ent, 

 and the emergence of an organism or a clone of cells with altered 

 properties. In between are many steps. The chemical has to pass 

 barriers of permeability; it may produce the actual mutagen by inter- 

 action with the cytoplasm; the initial lesion in the genetic material 

 may be restored or made permanent; chromosome breakage may be 

 followed by restitution or rearrangement; the mutated gene has to 

 create new biochemical pathways; the mutated cell has to multiply 

 in the face of competition from non-mutated cells. The same chemical 

 that produces a change in the DNA will often affect the course of these 

 intermediary events by reactions outside the DNA. 



What we know at present about the action of most mutagens is 

 little more than speculation. I think this is partly due to the concen- 

 tration of effort towards the one question, how does the mutagen 

 react with the DNA? I shall briefly discuss what is known about the 

 action of some groups of mutagens. 



Alkylating Agents 

 These include some of the most potent chemical mutagens — the 

 "mustards", characterized by the presence of one or several chloro- 

 ethyl groups, the epoxides, ethylene imines, methane sulphonates, 

 and /3-propiolactone. A great number of alkylating agents have been 

 synthesized for use in cancer therapy. The successful ones were sub- 

 sequently tested on Drosophila, mainly by Fahmy and Fahmy (35) 1 in 



^ee References, page 136. 



