GENETICS OF NEOPLASIA 263 



present. It was also evident that the absence of the genes did not result in the elimina- 

 tion of the virus through the production of antibodies. In the absence of the genes the 

 virus merely did not multiply and was lost through dilution either in the female or in 

 her offspring if they, too, lacked the necessary genes. 



BIOCHEMICAL PATHWAYS 



Thus far much of the analysis of the links in the chain of events leading from the 

 primary genie action to the final neoplasm has been directed toward those links nearer 

 the neoplasm. Before these pathways are completely understood, much study must be 

 devoted to the earlier links, many of which are on the biochemical level. Biochemical 

 genetics in the mouse and other laboratory mammals is lagging behind that in micro- 

 organisms and even that in man, but development of the field is now urgent; and, with 

 the background supplied by the studies with microorganisms, rapid progress should be 

 expected. 



Our highly inbred strains of mice used in cancer research should be characterized 

 by the enzymatic patterns of their tissues just as they are now characterized by their 

 types and incidences of tumors, or, on a lower level, by their histocompatibilities. 

 Much work has been done on enzymatic patterns of neoplasms versus the normal 

 tissue of origin, with emphasis on hepatoma versus hepatic parenchyma; but of greater 

 importance in the etiology of cancer is comparison of the enzymatic pattern of one 

 hepatic parenchyma which, because of its genotype, will eventually give rise to neoplasia, 

 with the pattern of another hepatic parenchyma which, because of its different geno- 

 type, has very little chance of developing a neoplasm. 



The identification of neoplasia with specific genes such as lethal yellow, which has a 

 pronounced effect on the occurrence of a number of tumors, offers the possibility of 

 associating specific enzymatic differences affecting neoplasia with specific genes. The 

 effect of lethal yellow on normal growth suggests basic differences in protein synthesis. 



GENETICS OF THE NEOPLASTIC CHANGE 



The neoplastic change in the cell is a heritable change in that it is continued 

 through successive cellular generations. With a broad concept of mutation including 

 changes in all hereditary material within the chromosomes, within cytoplasmic bodies, 

 and even within viruses which when introduced into a cell alter its genetic nature, one 

 must accept the hypothesis that a neoplasm arises from a somatic mutation. 



Since somatic cells could not be subjected to breeding experiments — the only way 

 in the past of studying mutations — approaches to a genetic analysis of the neoplastic 

 changes have been limited to certain statistical approaches and to studies of correlation 

 between mutagenic capacities of compounds and their carcinogenic capacities. Within 

 certain limits positive correlations between mutagenesis and carcinogenesis have been 

 obtained, 145 but as a whole this attack has not been too fruitful. Mutagenic studies 



