IV.
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173
merits may help us to give more precise statements concerning the
relation between activity of proteases and inhibition of growth. Progress
in this field might enable us at the same time to develop more rational
and precise methods for chemotherapy of tumours. A modern chemotherapist ought to profit from these differences in enzymatic and
morphogenetic activity and so be able to develop methods which
inhibit tumour tissues without considerable toxic side-effects. This may
be especially true for the many important pathways of the metabolism
of purines and proteins.
B. Cathepsins as Regulators of Growth in Normal and Tumour-bearing Rats
Our investigations on amphibians indicate a close correlation between
activation of cathepsins and inhibition of growth. Many different facts
favour our working hypothesis, these are that in amphibians several
biological factors (e.g. starvation, or thyroxin during metamorphosis)
as well as several morphostatic substances during regeneration, can
activate tissue proteases for a long period. During such a period of
activation, a regression of protein content in the respective organs, or
an inhibition of growth may take place. Further experiments are needed
to substantiate our working hypothesis in more detail.
From our results on regenerates of amphibians the question arises as
to whether regression of organ proteins and activation of proteases are
also coupled in mammals and whether regressing tumours which are
treated by morphostatic substances show a measurable increase in their
catheptic activity. A positive answer to this question might be a good
argument for attempting to induce further tumour regressions by
activated cathepsins. The work of Benz has given some results which are
in favour of our hypothesis. They are summarized in the following
sections.
1. Cathepsins in the Normal Organs of the Rat
It appeared desirable to determine quantitively the catheptic activity
of the different normal organs of rat. As homogenates of the organs were
sometimes only partially activated, we measured the catheptic activity
only in optimally activated solutions. Nitrocasein was used as substrate
and the nitrated protein fragments were directly determined photometrically after precipitation of the unsplit casein molecules (Fig. 11).
Cysteine was used as activator as it does not interfere with the colour
of the nitrated protein fragments. Only freshly-prepared homogenates
were used at a pH of 5 0 in the presence of acetate buffer. The particles
of the homogenates also carry some catheptic activity. All reaction
mixtures were incubated uniformly for 30 min because of the straight
ACTION OF MORPHOSTATIC SUBSTANCES
173
merits may help us to give more precise statements concerning the
relation between activity of proteases and inhibition of growth. Progress
in this field might enable us at the same time to develop more rational
and precise methods for chemotherapy of tumours. A modern chemotherapist ought to profit from these differences in enzymatic and
morphogenetic activity and so be able to develop methods which
inhibit tumour tissues without considerable toxic side-effects. This may
be especially true for the many important pathways of the metabolism
of purines and proteins.
B. Cathepsins as Regulators of Growth in Normal and Tumour-bearing Rats
Our investigations on amphibians indicate a close correlation between
activation of cathepsins and inhibition of growth. Many different facts
favour our working hypothesis, these are that in amphibians several
biological factors (e.g. starvation, or thyroxin during metamorphosis)
as well as several morphostatic substances during regeneration, can
activate tissue proteases for a long period. During such a period of
activation, a regression of protein content in the respective organs, or
an inhibition of growth may take place. Further experiments are needed
to substantiate our working hypothesis in more detail.
From our results on regenerates of amphibians the question arises as
to whether regression of organ proteins and activation of proteases are
also coupled in mammals and whether regressing tumours which are
treated by morphostatic substances show a measurable increase in their
catheptic activity. A positive answer to this question might be a good
argument for attempting to induce further tumour regressions by
activated cathepsins. The work of Benz has given some results which are
in favour of our hypothesis. They are summarized in the following
sections.
1. Cathepsins in the Normal Organs of the Rat
It appeared desirable to determine quantitively the catheptic activity
of the different normal organs of rat. As homogenates of the organs were
sometimes only partially activated, we measured the catheptic activity
only in optimally activated solutions. Nitrocasein was used as substrate
and the nitrated protein fragments were directly determined photometrically after precipitation of the unsplit casein molecules (Fig. 11).
Cysteine was used as activator as it does not interfere with the colour
of the nitrated protein fragments. Only freshly-prepared homogenates
were used at a pH of 5 0 in the presence of acetate buffer. The particles
of the homogenates also carry some catheptic activity. All reaction
mixtures were incubated uniformly for 30 min because of the straight