170 MUTATIONS 



If we consider the type of chemical mutagens that were discussed 

 yesterday by Dr. Auerbach, we find that for almost every type of 

 compound she discussed, which has been shown to be mutagenic or 

 to cause chromosome abnormalties without actual demonstration of 

 point mutations, there are closely related compounds in the world 

 of drugs which are used with greater or lesser frequency in man. 

 (Compounds discussed in this section are shown in Fig. 24.) 



Take the most striking example — the alkylating agents. Compounds 

 of this group are employed in the chemotherapy of certain kinds of 

 cancer. An interesting relationship exists between carcinostatic, muta- 

 genic, and (curiously) carcinogenic agents. Some substances have all 

 three of these actions (4,12,29). 



It is certainly possible that agents of this type may owe their 

 mutagenic and anticancer effects to the same or similar action, for 

 example, through interference with chromosome replication in the 

 cancer cells, which are characterized by a rapid growth rate. It is 

 clear, at any rate, that they do not uniquely attack cancer cells but 

 owe their major toxicity to the production of detrimental changes in 

 rapidly growing normal tissues, primarily the bone marrow and the 

 epithelium of the intestinal tract, which undergo continuous rapid 

 cell division. 



Those who hold to a somatic mutation theory of the origin of cancer 

 readily explain the similarities between carcinogenic and mutagenic 

 agents on the basis that the carcinogens can induce a somatic muta- 

 tion which leads to the development of a clone of cancerous cells. 



A final aside on the question of teratogenesis, i.e., the induction of 

 abnormalities in the developing fetus (31). A number of teratogens are 

 also known to be mutagens, and it is conceivable that in some cases 

 of teratogenesis (although this has never been proved), the develop- 

 mental abnormality results from somatic mutation at a critical time 

 in fetal development, so that particular organ systems are affected. 



In general, when cancer is treated with alkylating agents or other 

 compounds which are known to be mutagenic, the genetic hazard 

 can be discounted because the type of patient who is receiving the 

 treatment is generally beyond the reproductive age. However, there 

 are some instances, such as in Hodgkin's disease, where the individual 

 is often within the reproductive age. This suggests an area for in- 

 vestigation as to whether patients so treated and subsequently having 

 children can be shown to have had genetic damage induced. 



Here one knows that the alkylating agents do act upon the neo- 

 plastic cells, and there would seem to be no good reason to doubt 

 they also act upon the germ cells. 



