VI EFFECT OF EXTRINSIC FACTORS 627 



that regeneration possibly may be inhibited also at a later stage, between growth 

 and differentiation. 



It may prove diagnostic of inhibitors specific to different stages, that their effects 

 svimmate (Lehmann, ig54a), whereas those of agents specific to the same stage do 

 not. This may provide a valuable test since in fact the effects of all agents are 

 usually apparent at several stages, probably because of the sequential effects of the 

 initial action. Thus Thornton (1951) found abnormalities of differentiation in 

 beryllium-inhibited regenerates, probably because of deficiencies in the initial 

 blastema, themselves due to the impediment of a thick dermal barrier: this is 

 normalh' dissolved by overgrowing epidermis, previously activated by the wound- 

 factor, which is the component specifically sensitive to beryllium. 



One of the amino-ketones appears to inhibit not only cell-migration but also 

 cell-division (Lehmann, 1949) and it also inhibits the later growth of cells and 

 nuclei (Dettelbach, 1952). Colchicine affects the movements of cells to some 

 extent (Hadorn and Chen, 1953; Lehmann, 1954b) and it also inhibits the sprout- 

 ing of nerve-fibres (Hoffmann, 1952), causing them to degenerate (Flinker and 

 Sidman, 1953), just as it causes regression of amputated limbs (Thornton, 1943; 

 Liischer, 1946). Short-wave radiations and denervation similarly both inhibit 

 cell-division and promote regression. Colchicine has been found (Ebner and Streck- 

 er, 1 950) to affect nucleic acid-metabolism which again is very active in the func- 

 tioning and regeneration of nerves (Bodian, 1947). All three groups of agent 

 therefore may act primarily on the same stage. If so then their effects may be 

 expected not to summate. 



Lithium, which stands in the same chemical relationship to Na and K as beryl- 

 lium does to the other two key physiological cations, Mg and Ca, retards regener- 

 ation at low, and accelerates at higher temperature (Trampusch, 1951; Mifume 

 1953). Rulon (1948), also, observed paradoxical effects of lithium when applied 

 to planarians before or after amputation. It induces supernumerary eyes in regener- 

 ating planarians (Brondsted, 1942) which probably is the result of an initial 

 inhibition (Butler and Blum, 1955). Like beryllium (Dubois et al., 1949; Chevre- 

 mont and Firket, 1949) it inhibits key reactions in phosphorus-metabolism 

 (Runnstrom and Gustafson, 1951). Colchicine, also, acts upon P-metabolism 

 (Ebner and Strecker, 1950). 



Anaesthetics and other depressant substances inhibit regeneration (Morgulis, 

 1909; Bilski, 1926). Paulain (1938) found atropine to have an inhibitory action, 

 but his mathematical procedure when dealing with other depressants was not 

 suitable (p. 608) to detect possible effects. 



VII. INTERNAL FACTORS IN THE CONTROL OF REGENERATION 



[a] jSutrition and regeneration 



Except in studies on the mammals, little fractionation into dietary components 

 has been attempted, and it may be assumed provisionally that any observed 

 effects of quantitative variations in intake are due mainly to the protein-consti- 

 tuent. Adequate nutrition is essential for regeneration in mammals (Anon., 1953) 



Literature p. 64g 



