NEOPLASTIC ABNORMAL GROWTH 23Q 



into the cytoplasm of the former. Little (86) in a most significant ex- 

 periment crossed two species of mice, Mus bactrianus and C57 black 

 derived from Mus musculus. The two species differ markedly in size, 

 fertility, and rate of growth. The incidence of tumors in the Fi hybrids 

 was far greater than could be accounted for even by the addition of the 

 spontaneous tumor-forming tendencies of the parent strains. 



It is curious that this type of experiment has not been made more 

 frequently, since it is wholly in keeping with other evidence which has 

 accumulated concerning the development of neoplasms. The work with 

 the Shope papilloma virus in the induction of tumors in domestic rab- 

 bits clearly involves the introduction of a cellular protein constituent 

 from one species into the cells of another and not too closely related 

 species, with resultant tumor production and disappearance of the virus. 

 The studies of Claude (87) concerning the enzymatic activities of cer- 

 tain cytoplasmic granules suggest the possibility that such protein par- 

 ticles might modify genes if introduced into the cytoplasm of a cell of 

 another species. Since the genes produce enzymes (25), and modifica- 

 tion of enzymes can alter the source genes (51), and since one group of 

 chemical carcinogens form in their metabolism substances toxic to en- 

 zymatic activity (69), the route of both carcinogen and filterable factor 

 may be to the gene through the enzyme. This type of thought must be 

 considered as the wildest speculation, however, until much more evi- 

 dence is available. One would like to have precise data on the ability of 

 enzymes from one group of cells to affect the activity of enzymes from 

 another group, clear proof of a change from normal of the enzyme 

 activities of the cancer cell, more facts bearing on the participation of 

 the filterable tumor-producing agents in the activity of kinetically active 

 chemical systems, and finally a satisfactory demonstration of the ability 

 to alter genes by the introduction of different enzymes into a cell. 



The increased rate of tumor production by hybridization, like that by 

 carcinogenic chemicals in genetically suitable material (88), provides 

 another example of gene mutation caused by procedures also effective 

 in causing neoplastic disease. Sturtevant (21) proved that the offspring 

 of the back-crosses from hybrids between two races, A and B, of Dro- 

 sophila pseudoobscura show a very large increase in mutation fre- 

 quency. In this material 9% lethals and 0.5% of sex-linked viables 

 were produced without any evidence of increase in the number of major 

 chromosome aberrations like those resulting from x-radiation. This ex- 

 periment may be of great significance because it proves that mutations 

 can be caused without obvious morphological alteration of the geneti- 



