NEOPLASTIC ABNORMAL GROWTH 229 



which would cause gene mutation were actively sought, but clear proof 

 of their existence was lacking. More recently, however, a group of com- 

 pounds known as the halogenated tertiary alkyl amines (nitrogen mus- 

 tards) has been studied. From the effects of these substances on Dro- 

 sophila (53), on Neurospora (54), and on tobacco mosaic virus (55), 

 it is clear that they are effective in causing mutations of classic types, 

 it is interesting, furthermore, that they affect tissues in vivo very much 

 as x-rays do. Inhibition of mitosis, injury to intestinal epithelium, 

 damage to hematopoietic and lymphoid tissue, and necrosis of skin are 

 all eft'ects caused by both agents (56). Furthermore, the studies of 

 Bodenstein (57) reveal that the nitrogen mustards, applied to growing 

 tissue of the proper type and stage of development, stop cellular pro- 

 liferation and cause extensive swelling, possibly an effort toward differ- 

 entiation. This has also been shown by Karnofsky (58) in the Memo- 

 rial Hospital laboratories to be true for neoplastic cells of one type, 

 mouse sarcoma 180, grown on the chick embryo. 



Another set of genetically active chemical agents are the carcinogenic 

 substances of classic type containing a phenanthrene nucleus. When 

 applied to tissue they cause profound alterations of cells which lead to 

 self-reproducing alterations coincident with the assumption of neo- 

 plastic characteristics. Stowell (59) has shown that these changes are 

 associated with alterations of nucleic acid content and Biesele (20) has 

 demonstrated irregular alterations of chromosome structure. The 

 metabolic and chemical abnormalities of the cancer cells induced by 

 carcinogens have been so completely reviewed by Burk (60) and by the 

 students of the Cowdry school (61) as to leave little doubt of their 

 importance. 



Unfortunately, few data are at hand on the use of carcinogenic 

 chemical agents on material susceptible to genetic study. Beadle (25) 

 states that tests with these substances have not resulted in mutations. 

 Tatum (62) is said, however, to have made certain new observations 

 which provide acceptable evidence that mutations can be induced in 

 Neurospora by methyl-cholanthrene. Mottram (63) and Spencer and 

 his associates (126) have reported striking changes in protozoa, and 

 Strong (64) has recently published impressive studies on genetic 

 changes in mice which have resulted from the administration of the 

 same compound to young animals. Further work appears to be indicated. 



A possible explanation of the difficulty in causing mutations in 

 Neurospora by the chemical carcinogens is the fact that they are altered 

 by contact with body cells and that the active compounds are quite as 



