IV.
ACTION OF MORPHOSTATIC SUBSTANCES
159
substances, the regeneration is entirely suppressed. This takes place
beyond the range of toxicity of E 9 and colchicine. This observation gives
us a guiding idea for further experiments. If it is possible to affect
several partial morphogenetic processes by simultaneous or successive
applications of several inhibitors, then such a procedure considerably
increases the chances of depressing the morphogenetic potential of the
growing system and thus blocking regenerative processes entirely. Thus
a combined effect of a pair of morphogenetic inhibitors is essentially
increased without a sensible change in the toxic effects of the solutions
applied.
Our guiding idea concerning the increase of morphostatic effect by
pairs of synergistic substances has shown itself to be successful in
several experiments. Therefore we have also tried to modify biochemical
partial systems by chemical treatment. We were able to show that the
metabolism of proteins reacts to chemical treatment (Jensen, Lehmann
and Weber, 1956). There exist also many indications in the literature
that the metabolism of purines can be modified by suitable inhibitors.
Combined solutions such as aminoketones and colchicine appear from
a biochemical viewpoint to be very different metabolic and biological
inhibitors (v. Hahn and Lehmann, 1958).
1. Different Types of Morphostatic Substances
in Regeneration Experiments
After it had become evident from our experiments that inhibitors of
growth are not necessarily antimitotic substances, we studied primarily
such inhibitors as might be considered to be antimetabolites in the
metabolism of proteins or purines (Lehmann, 1957a). The following types
of morphostatic substances were studied.
(1) Inhibitors of regeneration which seem to interfere with protein
metabolism:
Aminoketone E 5 (Erlenmeyer); hydrochloride of dZ-3-amino-5-methylhexan-2-one (Lehmann et al., 1950).
Aminoketone E 9 (Erlenmeyer); hydrochloride of dl-5-amino-6-methylheptan-3-one (Lehmann et al., 1950; Lehmann, 1954).
Histidinol (aminoalcohol).
Tyrosinol (aminoalcohol).
Mercaptoethanol (unpublished data).
(2) Substances which seem to interfere with the metabolism of
purines (Lehmann, 1957a):
l,2-dihydro-3-methyl-7-ethoxyquinoxal-2-one. (Quinoxaline 3576, Ciba)
2,4-diamino-6-methylpteridine of Cyanamide Inc.
5,7-dimercapto-thiazolo-(5,4-d)-pyrimidine (E 9 6 ) (v. Hahn, Prijs and
Erlenmeyer, 1956).
ACTION OF MORPHOSTATIC SUBSTANCES
159
substances, the regeneration is entirely suppressed. This takes place
beyond the range of toxicity of E 9 and colchicine. This observation gives
us a guiding idea for further experiments. If it is possible to affect
several partial morphogenetic processes by simultaneous or successive
applications of several inhibitors, then such a procedure considerably
increases the chances of depressing the morphogenetic potential of the
growing system and thus blocking regenerative processes entirely. Thus
a combined effect of a pair of morphogenetic inhibitors is essentially
increased without a sensible change in the toxic effects of the solutions
applied.
Our guiding idea concerning the increase of morphostatic effect by
pairs of synergistic substances has shown itself to be successful in
several experiments. Therefore we have also tried to modify biochemical
partial systems by chemical treatment. We were able to show that the
metabolism of proteins reacts to chemical treatment (Jensen, Lehmann
and Weber, 1956). There exist also many indications in the literature
that the metabolism of purines can be modified by suitable inhibitors.
Combined solutions such as aminoketones and colchicine appear from
a biochemical viewpoint to be very different metabolic and biological
inhibitors (v. Hahn and Lehmann, 1958).
1. Different Types of Morphostatic Substances
in Regeneration Experiments
After it had become evident from our experiments that inhibitors of
growth are not necessarily antimitotic substances, we studied primarily
such inhibitors as might be considered to be antimetabolites in the
metabolism of proteins or purines (Lehmann, 1957a). The following types
of morphostatic substances were studied.
(1) Inhibitors of regeneration which seem to interfere with protein
metabolism:
Aminoketone E 5 (Erlenmeyer); hydrochloride of dZ-3-amino-5-methylhexan-2-one (Lehmann et al., 1950).
Aminoketone E 9 (Erlenmeyer); hydrochloride of dl-5-amino-6-methylheptan-3-one (Lehmann et al., 1950; Lehmann, 1954).
Histidinol (aminoalcohol).
Tyrosinol (aminoalcohol).
Mercaptoethanol (unpublished data).
(2) Substances which seem to interfere with the metabolism of
purines (Lehmann, 1957a):
l,2-dihydro-3-methyl-7-ethoxyquinoxal-2-one. (Quinoxaline 3576, Ciba)
2,4-diamino-6-methylpteridine of Cyanamide Inc.
5,7-dimercapto-thiazolo-(5,4-d)-pyrimidine (E 9 6 ) (v. Hahn, Prijs and
Erlenmeyer, 1956).