IV GROWTH OF TISSUES 1 65 



Experimental study supports this histological classihcation. Tissues with cell 

 renewal are characterized by a relatively high mitotic rate in the adult organism 

 which is balanced by a corresponding loss of cells, so that the total cell number 

 remains unchanged and neither positive nor negative growth takes place. A 

 frequently used technique (Leblond and Stevens, 1948; Storey and Leblond, 1951 ; 

 F. D. Bertalanffy and Leblond, 1953; Leblond and Walker, 1956) is the appli- 

 cation of colchicine which stops mitosis and allows counts of mitoses and hence 

 determination of mitotic rate over a period of time. A survey of cell renewal 

 in the principal mammalian organs is presented in Table 4 showing that tissues 

 such as intestinal epithelium, epidermis, and lung have a surprisingly high mitotic 

 rate and correspondingly rapid turnover and short time of renewal. It is worth 

 mentioning that although most investigations were carried out with mammalian 

 organs, the same principle applies to invertebrates. The adult hydra, for example, 

 remains in a steady state by continuous cell loss at the poles and corresponding 

 physiological regeneration by production of cells from the undifferentiated I-cells. 

 Amputation entails an increased cell production by the L cells and so restitution 

 of the steady state (Tardent, 1954). 



Obviously there are connections between the type of a tissue with respect to 

 its cell renewal, mitotic activity, turnover rate as determined by isotope labelling, 

 autolysis, and susceptibility to malignant transformation. It does not seem to be 

 possible, however, to reduce these correlations to a hard and fast rule. 



Protein turnover as determined by isotopes and other methods is only loosely 

 correlated with cell renewal of the tissue concerned. Corresponding to the high 

 renewal rate, high protein turnover is found in the intestinal mucosa, the bone 

 marrow, and in embryonic and malignant as compared to normal tissues 

 (Borsook, 1950). However, functional activities must also be taken into considera- 

 tion as, for example, in the liver, which shows mitotic activity only in regeneration 

 (compensatory hyperplasia) but has a high protein turnover; or in nervous tissue 

 which represents a cell-constant organ with no mitotic activity, but has a high 

 content in RNA (Nissl bodies) and a rather high protein turnover (Weiss and 

 Hiscoe, 1948). 



A good correlation is found between classification of tissues in terms of presence 

 or absence of cell renewal, and experiments with 32p (Smellie, 1955). With 

 respect to incorporation of radiophosphorus into DNA, two main classes of tissues can 

 be distinguished: Bone narrow, spleen, thymus, and intestinal mucosa are 

 proliferating tissues where correspondingly incorporation of the isotope is high; 

 liver, kidney, and brain are organs with minimal or no cell division in the adult 

 organism, and correspondingly minimal ^^p incorporation into DNA. According 

 to expectation, increased incorporation is also found in regenerating rat liver, 

 in hepatoma, carcinomas, and the mammary gland during pregnancy. 



In order to maintain the steady state, there must be a harmonization between cell 

 loss and cell renewal. This is found experimentally: In the starved mouse, mitotic 

 rate of the epidermis is reduced by 25 per cent, although neither the thickness 

 of the epidermis nor the size of the sebacious glands is reduced. Obviously the 

 desquamation of the stratum corneum and the secretion of sebum must be 

 regulated accordingly (Bullough, 1952). 



Literature p. 253 



