IV REGULATING FACTORS OF THE PFS 527 



formation and formation of specific cell proteins, the present case would seem to 

 conform most closely to the situation of a decreasing total protein formation with the 

 specific proteins maintaining a high rate of accumulation. This could actually mean 

 that small quantities of specific proteins are formed even during the early phases of 

 development. Since, during this period, the production of proteins necessary for cell 

 proliferation is so rapid, the capacity of the PFS to form larger amounts of specific 

 proteins remains restricted to a very small fraction of the total protein production. 

 In fact, with enzymatic methods, very small quantities of such proteins have been 

 detected in very early phases of development which would support this suggestion 

 (Boell and Shen, 1944). Following this reasoning, diflferentiation would consist 

 not in the formation of protein species completely de novo but merely in an increased 

 rateof their production relative to the formation of other protein species. Parallel 

 observations from the field of microbiology are discussed below. It is not suggested 

 that such a mechanism operates in all types of cytodifferentiation. Although it 

 could hold for a number of cell types, the possibility of a true de novo synthesis of 

 certain proteins in some organs (lens proteins) can not be dismissed (Ten Gate and 

 Van Dooremaalen, 1950; Edds, 1958). 



For a study of the relationship between proliferation and diflferentiation in 

 mammalian tissues the rat liver seems to oflfer interesting possibilities (Eliasson, 

 Hammersten, Richard, Aqvist, Thorell and Ehrensvard, 195 1). After removal of 

 about two-thirds of the liver of the adult rat, regeneration to about the original 

 size of the organ takes place within 6-8 days. At the end of the first day of regener- 

 ation there is a large increase in mitotic activity and growth of the organ is 

 primarily due to cell proliferation. At the end of the second day mitotic activity has 

 fallen almost to its initial value and growth must be primarily due to production 

 of cytoplasmic material without significant proliferative activity. Within this 

 regenerative period there is a rapid transition from an actively proliferating tissue 

 to one which is growing by elaboration of specific cell products. The first prolifer- 

 ative period in liver regeneration is accompanied by a marked increase in the 

 quantities of both DNA and RNA (in absolute figures as well as relative to dry 

 weight) and in the incorporation of labelled glycine into nucleic acids. The rate 

 of incorporation of labelled amino acids into proteins increases rapidly during 

 xtie first day. From the 2nd day on the increase in incorporation is slower and 

 reaches a peak on the third day followed by a slow decrease in the incorporation 

 rate. 



In contrast, the concentration of apyrase and rhodanase per g protein begins 

 to fall when the total protein of the regenerating liver increases (Rosenthal, Rogers, 

 Vars and Ferguson, 1 95 1 ) . A similar fall was also observed (Novikoflf and Potter, 

 1948) for the enzymes succinoxidase, malic dehydrogenase and cytochrome reduc- 

 tase. Since all five enzymes are involved in specific functions of the diflferentiated 

 tissue these findings may mean that in regeneration actually a part of the specific 

 cell products (enzymes) is lost during the proliferative phase of growth. 



Another promising object for a study of the relation of growth and diflferentia- 

 tion is the red blood cell (Thorell, 1947; Thorell, 1953; Hammarsten, Thorell, 

 Aqvist, Eliasson and Akerman, 1953). In the mature erythrocyte a large fraction 

 of the total protein moiety consists of hemoglobin which represents the specific 



Literature p. ssg 



