IV.
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183
metabolism deserves attention because of its close relation to protein
metabolism and to the morphogenetic potential.
The recent findings of Van R. Potter are in accord with our considerations. In butter yellow induced tumours there is one enzyme
system lacking which attacks thymidine catabolically. Consequently
since thymidine is not broken down but stored in the deficient cells it
induces an excessive production of DNA. This in turn leads to a high
production of proteins and brings about a high proliferation rate of
cells. In this case products of purine metabolism interfere with the
anabolic side of protein metabolism. An increase of the morphogenetic
potential may presumably be the consequence and explain a more
intense growth of the tumour.
4. Protein Degradation and the Protein Supply of Growing Tissues
A third way to influence the protein metabolism is by the direct
increase of the activity of tissue proteases which might cause protein
degradation, regression of organs or inhibition of regeneration. It has
not so far been possible to decide whether the increase of activity found
in our experiments is caused by an increased number of enzyme
molecules or by intensified formation of enzyme activators. In many
cases the increase in activity of cathepsins seems to have important
normal functions such as the creation of a usable protein reserve. This
is certainly the case in starving tadpoles and tumour-bearing rats. The
tumour behaves as a biological 'protein parasite' and creates a deficiency
of proteins. In this case the activated cathepsins contribute essentially
to the mobilization of reserve proteins from the normal organs. Very
surprising to a developmental biologist is the phenomenon that normally
built and normally functioning organs can be forced to decrease their
own proteins. From the point of view of the physiology of nutrients, a
regulatory mechanism which mobilizes organic reserve materials seems
to be conceivable. Also the results of many earlier starvation experiments
substantiate our explanation.
It seems quite characteristic that a growing tumour does not respond
to regulatory informations from the host organism. The tumour behaves
constantly as a 'nitrogen trap' and remains a parasite which does not
respond to correlating factors. The behaviour of the tumour cathepsins
is also very conclusive. The periphery of the Walker Carcinoma is rich
in cathepsins presumably in connection with its high intensity of cell
proliferation. This has nothing to do with the necrotic content of the
tumour. As a typical parasite the tumour is unable to utilize the dead
cell material. This remains purely waste material for the tumour as well
as for the host organism.
In a regressing tumour another picture dominates. The catheptic
ACTION OF MORPHOSTATIC SUBSTANCES
183
metabolism deserves attention because of its close relation to protein
metabolism and to the morphogenetic potential.
The recent findings of Van R. Potter are in accord with our considerations. In butter yellow induced tumours there is one enzyme
system lacking which attacks thymidine catabolically. Consequently
since thymidine is not broken down but stored in the deficient cells it
induces an excessive production of DNA. This in turn leads to a high
production of proteins and brings about a high proliferation rate of
cells. In this case products of purine metabolism interfere with the
anabolic side of protein metabolism. An increase of the morphogenetic
potential may presumably be the consequence and explain a more
intense growth of the tumour.
4. Protein Degradation and the Protein Supply of Growing Tissues
A third way to influence the protein metabolism is by the direct
increase of the activity of tissue proteases which might cause protein
degradation, regression of organs or inhibition of regeneration. It has
not so far been possible to decide whether the increase of activity found
in our experiments is caused by an increased number of enzyme
molecules or by intensified formation of enzyme activators. In many
cases the increase in activity of cathepsins seems to have important
normal functions such as the creation of a usable protein reserve. This
is certainly the case in starving tadpoles and tumour-bearing rats. The
tumour behaves as a biological 'protein parasite' and creates a deficiency
of proteins. In this case the activated cathepsins contribute essentially
to the mobilization of reserve proteins from the normal organs. Very
surprising to a developmental biologist is the phenomenon that normally
built and normally functioning organs can be forced to decrease their
own proteins. From the point of view of the physiology of nutrients, a
regulatory mechanism which mobilizes organic reserve materials seems
to be conceivable. Also the results of many earlier starvation experiments
substantiate our explanation.
It seems quite characteristic that a growing tumour does not respond
to regulatory informations from the host organism. The tumour behaves
constantly as a 'nitrogen trap' and remains a parasite which does not
respond to correlating factors. The behaviour of the tumour cathepsins
is also very conclusive. The periphery of the Walker Carcinoma is rich
in cathepsins presumably in connection with its high intensity of cell
proliferation. This has nothing to do with the necrotic content of the
tumour. As a typical parasite the tumour is unable to utilize the dead
cell material. This remains purely waste material for the tumour as well
as for the host organism.
In a regressing tumour another picture dominates. The catheptic