IV.
ACTION OF MORPHOSTATIC
SUBSTANCES
155
much valuable information on partial inhibitory effects. The results of
tumour biology so far achieved strongly demonstrate the need for
greater co-operation with developmental biology. It is the aim of the
following chapter to show that a detailed application of the knowledge
of developmental biology and enzymology may stimulate new lines of
thought and experimentation in tumour research.
For the developmental biologist it is of great value to know that there
are at present very few single chemical substances which act selectively
on tumour growth in warm blooded animals (Farber et al., 1956;
Loustalot, 1957). We have made a parallel statement about the biology
of regeneration. We investigated numerous substances which partially
inhibit the regeneration of the amputated tail tip in Xenopus larvae. We
have found only relatively few substances (i.e. colchicine, a quinoxaline
compound and a few aminoketones) which suppress regeneration totally
(Lehmann, 1957b; Lehmann and Bretscher, 1952;Dettelbach, 1952). But
the total morphostatic action of these substances ranges so near to the
limits of toxicity that they cannot be used as single inhibitory substances
in tumour biology.
A. Selective Suppression of Regenerative Growth
by Pairs of Morphostatic Substances
Our detailed investigations are in accord with A. E. Needham's
(1952) general review of regeneration. It has been found by us that the
regeneration of the amputated tail of the anuran tadpole is a very complex process in which different partial processes, like cell migration,
cell division, growth and differentiation of regenerated tissues are intricately interwoven. We have found in different instances that several inhibitory substances may act in a different and characteristic way on
different partial processes, whereas other processes may continue without visible abnormalities (Lehmann, 1957b). Blocking of partial processes
very rarely leads to total suppression of regeneration (Fig. 1(6)). In this
observation may lie a plausible reason for the frequent failure of tumour
chemotherapy with single substances. Such partial inhibitors may influence strongly a single process but may not be able to suppress the
total activity of a complex growing system.
In consequence we tried to produce much stronger morphostatic
effects by interfering with two or more independent morphogenetic
activities. To this end we used the aminoketone E 9 (Erlenmeyer, c/.
Lehmann, Bretscher et al., 1950) which inhibits cell activation and
migration and colchicine which blocks subsequent cell movements and
mitotic divisions. The combination of the two inhibitors appeared to act
in a highly synergistic way (Table I). By suitable concentrations of both
ACTION OF MORPHOSTATIC
SUBSTANCES
155
much valuable information on partial inhibitory effects. The results of
tumour biology so far achieved strongly demonstrate the need for
greater co-operation with developmental biology. It is the aim of the
following chapter to show that a detailed application of the knowledge
of developmental biology and enzymology may stimulate new lines of
thought and experimentation in tumour research.
For the developmental biologist it is of great value to know that there
are at present very few single chemical substances which act selectively
on tumour growth in warm blooded animals (Farber et al., 1956;
Loustalot, 1957). We have made a parallel statement about the biology
of regeneration. We investigated numerous substances which partially
inhibit the regeneration of the amputated tail tip in Xenopus larvae. We
have found only relatively few substances (i.e. colchicine, a quinoxaline
compound and a few aminoketones) which suppress regeneration totally
(Lehmann, 1957b; Lehmann and Bretscher, 1952;Dettelbach, 1952). But
the total morphostatic action of these substances ranges so near to the
limits of toxicity that they cannot be used as single inhibitory substances
in tumour biology.
A. Selective Suppression of Regenerative Growth
by Pairs of Morphostatic Substances
Our detailed investigations are in accord with A. E. Needham's
(1952) general review of regeneration. It has been found by us that the
regeneration of the amputated tail of the anuran tadpole is a very complex process in which different partial processes, like cell migration,
cell division, growth and differentiation of regenerated tissues are intricately interwoven. We have found in different instances that several inhibitory substances may act in a different and characteristic way on
different partial processes, whereas other processes may continue without visible abnormalities (Lehmann, 1957b). Blocking of partial processes
very rarely leads to total suppression of regeneration (Fig. 1(6)). In this
observation may lie a plausible reason for the frequent failure of tumour
chemotherapy with single substances. Such partial inhibitors may influence strongly a single process but may not be able to suppress the
total activity of a complex growing system.
In consequence we tried to produce much stronger morphostatic
effects by interfering with two or more independent morphogenetic
activities. To this end we used the aminoketone E 9 (Erlenmeyer, c/.
Lehmann, Bretscher et al., 1950) which inhibits cell activation and
migration and colchicine which blocks subsequent cell movements and
mitotic divisions. The combination of the two inhibitors appeared to act
in a highly synergistic way (Table I). By suitable concentrations of both