CARCINOGENESIS 



conversion of a normal cell to a cancer cell might simply be con- 

 sidered but another expression of the same process more 

 clearly typified by the conversion of a streptomycin-sensitive 

 strain of bacteria to a streptomycin-resistant strain. But these 

 hypotheses still remain to be established. They are, however, 

 becoming more amenable to testing in higher animals because 

 of the manifold possibilities for studying the metabolism of 

 tumors and normal tissues by means of isotopic tracers, and such 

 work forms a significant proportion of the present research at 

 the McArdle Memorial Laboratory (28,40,41,59,60). This 

 concept of evolutionary change is applicable not only to the 

 conversion of normal cells to cancer cells or to the individual 

 stages in this process, but also to the conversion of drug-sensitive 

 cancer cells to drug-resistant cancer cells. This process has 

 been studied intensively in leukemic cells at the National Cancer 

 Institute by Law (37), who has emphasized that the conversion 

 is mainly a process of natural selection, in which a few resistant 

 or dependent mutants survive and become the basis of a new line, 

 while the sensitive cells are eliminated. 



Ideas on the conversion of normal cells to cancer cells stem 

 from the newer knowledge of how one cell type is transformed to 

 another. These ideas are at present in a state of ferment, and 

 great changes are occurring in some of the concepts of hereditary 

 mechanisms. What was once regarded only in terms of muta- 

 tions of nuclear genes and the resultant Mendelian heredity can 

 now be considered in the light of at least four clear-cut extra- 

 Mendelian mechanisms for changing the metabolic pattern of a 

 cell. These are: 



7. Hereditary change by cytoplasmic segregation. This change is 

 the result of the continued division of cells at a rate that outpaces 

 the formation of cytoplasmic particles, leading to the loss of such 

 particles by simple dilution. Thus, those enzymes whose for- 

 mation is controlled by these particles will be lost. Observa- 

 tions of this nature have been made by Sonneborn (62), 

 Ephrussi (17,18), Spiegelman (64), and others (34,77). 



2. Partial hereditary transfer {genetic transduction) by deoxyri- 



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