EXPERIMENTAL MAMMALIAN TERATOLOGY 235 



used. Second, there is the possibility that some factor in the experimental procedure 

 other than the teratogen being studied may itself be teratogenic. For instance, some 

 teratogenic procedures may be so stressful to the mother that she will stop eating 

 during the treatment, and maternal fasting is itself teratogenic in some situations. 

 Third, there are a number of variables such as maternal weight, 677 diet, 1190 and season 

 of the year 629 that have been related to the frequency of malformations, and these must 

 be taken into account when comparing the results of different series. Finally, there 

 are genetic differences between strains and substrains that demand caution in com- 

 paring results from different laboratories, or even from the same laboratory at different 

 times. 



AGENTS USED FOR TERATOLOGIC STUDIES 



There are now on record a great number of agents with teratogenic properties. 

 Those that can be classed as metabolic (which includes nearly all of them except 

 irradiation) have been discussed recently by Kalter and Warkany 681 in an exhaustive 

 and useful review. It is difficult to classify teratogens in any logical way, since the 

 modes of action of most of them are not accurately known ; for instance, agents usually 

 considered as physical may act through biochemical pathways and vice versa. Wil- 

 son 1392 has grouped teratogens acting in mammals under the headings of physical 

 agents (X rays, hypothermia, hypoxia, elevated C0 2 , puncture of amniotic sac) ; 

 maternal nutritional deficiencies (lack of vitamin A, riboflavin, folic acid, pantothenic 

 acid, vitamin B12, thiamine, and vitamin D, and fasting); growth inhibitors and 

 specific antagonists (nitrogen mustard, thiadiazole, triazines, other alkylating agents, 

 urethan, azaserine, 6-aminonicotinamide, 8-azaguanine, thioguanine, 6-mercap- 

 topurine, 2-6-diaminopurine, 6-chloropurine), infectious agents (influenza-A virus, 

 attenuated hog-cholera virus, Newcastle virus) ; hormone excesses and deficiencies 

 (androgens, estrogens, insulin, cortisone, vasopressin, adrenalin, alloxan diabetes) ; 

 and miscellaneous drugs and chemicals (trypan blue, excess of vitamin A, antibiotics, 

 chelating agents, phenylmercuric acetate, nicotine, salicylates). 



Choice of a teratogen depends on the purpose of the investigator. One may wish 

 to know, for instance, whether a particular drug, or other environmental agent, may 

 be teratogenic in humans. In this case the choice of teratogen is decided by the 

 experimenter's question. If the investigator wishes to study the pathogenesis of a 

 particular malformation, he will wish to choose a teratogen which, in the appropriate 

 organism, will produce a high frequency of the malformation to be studied. In this 

 way he can be relatively sure that the embryo examined during early development 

 would have been malformed at birth. Alternatively, he may prefer to study the 

 arrays of malformations produced by exposure to the teratogen at various embryonic 

 stages, on the assumption that the types of malformations produced by teratogens 

 with various metabolic effects may yield information about the nature of the develop- 

 mental mechanisms involved. 



