626 REGENERATION AND GROWTH 7 



ble service in the analysis of ontogenesis is due to lithium salts (Lehmann, 1945). 

 Some other agents used also are already known to affect normal growth, and in- 

 clude colchicine and nitrogen-mustards. Lehmann (1954) has initiated a more 

 rational approach by the use of antagonists of specific metabolites and, in conse- 

 quence perhaps, has produced effects with a high degree of specificity to particu- 

 lar stages of regeneration. Thus the amino-ketone, and other, analogues of the 

 amino acids leucine, valine, tyrosine and histidine, inhibit relatively specifically 

 the cell-migrations leading to formation of a blastema (Liischer, 1946; Lehmann 

 and Dettelbach, 1952; Hadorn and Chen, 1953; Lehmann, 1954a). The subse- 

 quent stage of cell-proliferation is no longer sensitive (Dettelbach, 1952). Cobalt 

 salts, which form a complex with histidine, also inhibit at this stage (Lehmann, 

 1954a). Additional leucine does not prevent the action of its amino-ketone ana- 

 logue (Lehmann, 1949) possibly because peptides, rather than free amino acids, 

 are the active agents (Liischer, 1952). Glucosamine, also, inhibits cell-migrations 

 (Lehmann, iq54a), possibly as a partial analogue of amino acids or because, as 

 a product of the breakdown of the mucoproteins, it inhibits the normal break- 

 down of these proteins in connective-tissue barriers. Tuchmann-Duplessis (1950) 

 finds that beryllium salts also inhibit at this stage and this is consistent with the 

 results of Thornton (1951). Epidermal cells fail to cover the wound, which usually 

 reopens (Thornton, 1951), and causes a second phase of dedifferentiation. Further, 

 mesodermal blastema-cells fail to accumulate (Thornton, 1951) possibly owing to 

 the lack of a normal stimulus from active epidermis (Polezhayev and Favorina, 

 1935; Lehmann, personal communication). Once the blastema is established, 

 regeneration is no longer inhibited by beryllium which, in fact, must act within 

 a few minutes of amputation, in Amphibia (Needham, 1941; Thornton, 1949). 

 Epidermal cell-migration therefore is normally induced at a very early stage by 

 the wound-factor (p. 637). Arthropods, by contrast, do not produce a wound- 

 factor, and the stump of an amputated limb of the Isopod, Asellus, is much more 

 resistant to the action of beryllium than that of an amphibian. To induce sub- 

 stantial retardation, — 45% of the rate of the partner control limb — by a brief 

 exposure of 30 sec, it was necessary to use a 20% concentration of BeClj, effectively 

 an histological fixative. At this concentration it was not much more inhibitory 

 than equimolar HCl (39%) or a saturated solution of lead acetate (27%), though 

 its action was more persistent. 



Colchicine is fairly specific to cell-division (Thornton, 1943; Liischer, 1946; 

 Lehmann, 1949), and so are nitrogen mustards (Supniewski, 1949; Skowron and 

 Roguski, 1953), as in normal growth. Colchicine acts mainly on the division- 

 spindle and the mustards on the chromosomes. A number of basic dyes also are 

 specific to cell-division (Steinmann and Wilhelmi, 1950) and alizarin even to one 

 cell, the osteoblast (Eksterowicz, 1950). Colchicine behaves very similarly (p. 624) 

 to other antimitotic agents (Thornton, 1943). Some other aromatic ketones, struc- 

 turally related to colchicine, also inhibit cell-division, in the tail-regenerate of 

 Xenopus-ta.dpo\es (Lehmann, 1 954)0). 



Certain quinoxalins appear to inhibit at a stage between cell-proliferation and 

 histodifferentiation (Lehmann and Dettelbach, 1952), presumably the stage of 

 cell-hypertrophy, while other technic^ues (De Giorgi and Guyenot, 1923) indicate 



