IV.
ACTION
OF MOEPHOSTATIC SUBSTANCES
167
1957; Weber, 1957a, b; Benz, 1957; v. Hahn and Lehmann, 1958). In our
cases a strong activation of cathepsin was induced. A decrease of proteins
eventually resulted together with reduction of organ size or with strong
inhibition of growth in the case of regeneration. We suppose at least
for some cases that several morphostatic substances inhibit growth by
activating excessively the cathepsin systems. This chain of reactions
might offer a model type of growth inhibition by purely metabolic
factors in which neither abnormalities of mitosis nor heavy cytoclastic
effects are involved. From this we gain another guiding idea for the
experimental inhibition of regenerates or growth, i.e. inhibition of
growth of regenerates or tumours simply by activation of proteindecomposing enzyme systems such as the cathepsins. Analogous
considerations have been published already for the metabolism of
purines and nucleotides (Potter, 1959). They too seem to offer very
interesting perspectives.
A. Morphostatic Substances as Inhibitors of Regenerative Growth
and as Activators of Tissue Proteases (Cathepsins)
1. General Remarks
v. Hahn has tested experimentally our guiding idea concerning the
'inhibition of regenerative growth by synergistic inhibiting substances
and the ensuing activation of cathepsins.' He studied in detail the
actions of the morphostatic aminoketone E 9 and colchicine in synergistic
combination on the regeneration of the amputated tail tip of Xenopus
larvae and its intercellular proteases (v. Hahn, 1959).
2. Material and Methods
The culture methods for the larvae and the detailed experimental
procedure are given by H. P. von Hahn and F. E. Lehmann (1958).
With casein as substrate the activity of the tail cathepsins is found by
the use of the phenol reagent of Folin-Ciocalteu to determine the
cleavage products. The total nitrogen is obtained with the ultramicroKjeldahl method of Boell & Shen (1954). Aminoketone E 9 (4-amino-6methyl-heptan-3-one hydrochloride) and colchicine are quite soluble in
water. They were used for single application in concentrations of
1 : 8,000 (E 9 ) and 1 : 2,000,000 (colchicine). In the combined solutions
the concentrations were 1 : 32,000 and 1 : 4,000,000 respectively. The
concentrations applied were so chosen that the regeneration was
expected to be inhibited approximately 50%. 8 mm. of the larval tail
tip was amputated (Fig. 6(a)). For each experiment the following controls
were prepared: non-amputated animals in solution of the morphostatic
substance and in water (controls for cathepsin) and amputated animals
ACTION
OF MOEPHOSTATIC SUBSTANCES
167
1957; Weber, 1957a, b; Benz, 1957; v. Hahn and Lehmann, 1958). In our
cases a strong activation of cathepsin was induced. A decrease of proteins
eventually resulted together with reduction of organ size or with strong
inhibition of growth in the case of regeneration. We suppose at least
for some cases that several morphostatic substances inhibit growth by
activating excessively the cathepsin systems. This chain of reactions
might offer a model type of growth inhibition by purely metabolic
factors in which neither abnormalities of mitosis nor heavy cytoclastic
effects are involved. From this we gain another guiding idea for the
experimental inhibition of regenerates or growth, i.e. inhibition of
growth of regenerates or tumours simply by activation of proteindecomposing enzyme systems such as the cathepsins. Analogous
considerations have been published already for the metabolism of
purines and nucleotides (Potter, 1959). They too seem to offer very
interesting perspectives.
A. Morphostatic Substances as Inhibitors of Regenerative Growth
and as Activators of Tissue Proteases (Cathepsins)
1. General Remarks
v. Hahn has tested experimentally our guiding idea concerning the
'inhibition of regenerative growth by synergistic inhibiting substances
and the ensuing activation of cathepsins.' He studied in detail the
actions of the morphostatic aminoketone E 9 and colchicine in synergistic
combination on the regeneration of the amputated tail tip of Xenopus
larvae and its intercellular proteases (v. Hahn, 1959).
2. Material and Methods
The culture methods for the larvae and the detailed experimental
procedure are given by H. P. von Hahn and F. E. Lehmann (1958).
With casein as substrate the activity of the tail cathepsins is found by
the use of the phenol reagent of Folin-Ciocalteu to determine the
cleavage products. The total nitrogen is obtained with the ultramicroKjeldahl method of Boell & Shen (1954). Aminoketone E 9 (4-amino-6methyl-heptan-3-one hydrochloride) and colchicine are quite soluble in
water. They were used for single application in concentrations of
1 : 8,000 (E 9 ) and 1 : 2,000,000 (colchicine). In the combined solutions
the concentrations were 1 : 32,000 and 1 : 4,000,000 respectively. The
concentrations applied were so chosen that the regeneration was
expected to be inhibited approximately 50%. 8 mm. of the larval tail
tip was amputated (Fig. 6(a)). For each experiment the following controls
were prepared: non-amputated animals in solution of the morphostatic
substance and in water (controls for cathepsin) and amputated animals