NEOPLASTIC ABNORMAL GROWTH 233 



may be transient, and if so are usually a direct effect of environment 

 and return to normal if the environmental alteration is removed; or 

 they may be permanent, of a type for which no environmental cause 

 can be found. It may be assumed that these permanent changes are 

 analogous to the spontaneous mutations which occur in sexual forms. 

 A third type of variation occurs during the growth cycle, and may be 

 analogous to the changes leading to differentiation in more complex 

 cells. 



The changes which are transmitted by the altered cell to its progeny 

 are termed discontinuous variations and include certain of the consti- 

 tutive enzymes. The classical variation of this type is the unexplainable 

 occurrence of lactose-fermenting forms of E. coli mutabile, normally 

 a non-lactose-fermenting organism. It has been shown by Lewis (74) 

 that all colonies of this organism generate about the same number of 

 variant cells, but so few as to escape detection by conventional methods. 

 The variation may occur in the absence of lactose. 



Dubos (73) states that in bacterial cultures non-beneficial variations 

 such as inadequate utilization of nutrients can be eliminated by over- 

 growth of the more vigorous original cells. This statement is an impor- 

 tant one, since it should also apply to the more complex cells of tissues. 

 However, normally it would not do so in the case of handicapping 

 variations of differentiated tissue cells because, in contrast to movable 

 bacteria, tissue components remain fixed in their relative positions. The 

 differentiated cell, which perhaps has normally mutated, becomes spe- 

 cialized in its function, loses its adaptability, and has to compete only 

 with similarly specialized cells adjacent to it. The most adult do not 

 come in direct contact with the young and particularly vigorous cells, 

 and so do not compete under the handicap imposed by the greater 

 adaptability of primitive forms. Thus, in tissue, cells limited to new 

 and specialized functions, such as seem to appear during differentiation, 

 are protected in their existence unless there develop in their midst more 

 competent and adaptable forms, such as neoplastic cells may be. 



The development of abnormal cells in tissues can be caused experi- 

 mentally by the application of certain agents as specified previously. 

 All of these cause mutations, and all have a pronounced toxic or inhibi- 

 tory effect on the normal cells with which they come in contact, with 

 the result that the pathological forms, characteristic of neoplasm, ap- 

 pear. Perhaps analogous to this development of cancer following the 

 prolonged intoxication of normal cells are the discontinuous variations 

 of bacteria which yield abnormal cells characterized by their resistance 



