EXPERIMENTAL MAMMALIAN TERATOLOGY 245 



of the palatine shelves from the vertical to the horizontal plane was the cause of the 

 clefts observed at birth. 1354 Furthermore, comparison of the normal time of palatal 

 closure in these strains and crosses showed a correspondence between the normal time 

 of palatal closure and the frequency of induced cleft palate, thus demonstrating how a 

 genetically determined difference in normal developmental pattern was related to the 

 observed differences between strains in response to the teratogen. 



Differences between inbred strains in response to teratogens can also be useful in 

 elucidating the metabolic pathways involved. For instance, the frequency of cleft 

 palate produced by a transitory inactivation of nicotinamide is higher in the A/Jax 

 strain than in the C57BL/6 strain, and in the A/Jax x G57BL/6 than in the C57BL/6 x 

 A/Jax hybrids, 448 just as it is when cortisone is used as a teratogen. On the other hand, 

 galactoflavin produces more cleft palates in the C57BL/6 strain than in the A/Jax 

 strain. 680 This shows that the susceptibility of the A/Jax palate to cortisone and 6-AN 

 is not just a nonspecific instability to any environmental insult. It also suggests that 

 galactoflavin interferes with closure of the palate at a different metabolic point than 

 cortisone and 6-AN, and that perhaps cortisone and 6-AN act on the same pathway. 

 Since 6-AN is known to interfere with DPN synthesis, this implies that cortisone's 

 teratogenicity may reside in its effect on DPN synthesis, or on some related process. 

 Of course we would not want to draw conclusions from these few comparisons, but the 

 approach appears useful. By observing the effects of a variety of teratogens on a panel 

 of strains and seeing which ones produce the same patterns of strain differences in 

 frequency of malformation, it should be possible to deduce which ones are affecting 

 the same metabolic pathways, and get some idea of which pathways are involved. 



SUMMARY 



This review of methodology in experimental mammalian teratology has con- 

 sidered the following aspects: choice of experimental animal, choice of teratogen, 

 gestational stage of treatment, dose of teratogen, and contributions of teratologic studies 

 to a better understanding of the causes of malformations. 



Possible ways in which teratological methods can make such contributions include : 



1. Experimental screening for teratogenicity of agents suspected of causing 

 malformations in human beings. 



2. Production of specific malformations with known and controllable frequencies, 

 permitting embryologic studies of the pathogenetic processes leading to the defects 

 observed at birth, and testing of diagnostic and therapeutic procedures on malformed 

 animals. . 



3. The use of antimetabolites and immunologic preparations to study the bio- 

 chemistry of morphogenetic processes and the biochemical pathways through which 

 teratogens act. 



