GROWTH INDUCED BY DAMAGE
35
This might be possible since others, who have looked for either stimulators or inhibitors in tissue extracts, have usually found both (SzentGyorgyi et al., 1962; Teir, 1952). This raises the question if there is any
evidence that stimulators may be responsible for the initiation of damageinduced growth.
The literature on the presence of stimulators in cells is enormous
(Abercrombie, 1964; Arey, 1936; Goss, 1964; Loofbourow, 1948; Needham, 1960; Swann, 1958; Washburn, 1960). However the evidence that
stimulators are responsible for damage-induced growth is not compelling.
There has been no serious detailed study of the role of stimulators for
initiating damage-induced growth as there has been by Bullough for
inhibitors. So far the best evidence that stimulators may be involved in
initiating damage-induced growth has been the evidence of Argyris and
Trimble (1964a,b) that the loss of mass and presumably an inhibitor is
not a sufficient cue for initiating growth. But this evidence is strictly
indirect. Recently, Hell (1966) has found that TCA-soluble substances
from epidermal extracts of guinea pig epidermis can stimulate the uptake
of tritiated thymidine in guinea pig epidermal cells in vitro. The isolation
must be done quickly, using serum, and in the cold. The epidermis must
be kept in serum, otherwise activity is lost. This observation is very
important because these substances stimulate epidermal cells to enter
mitosis in the Gi phase of the cell cycle. Such substances could have
general significance for the problem of growth control. The confirmation
and extension of this study may mark the beginning of the definition of
the role of tissue stimulators in the initiation of damage-induced growth.
Thus, the scanty information on the molecular biology of damageinduced growth indicates that both stimulators and inhibitors have been
found in tissues. Each might be (or might not be) significant in the
initiation of damage-induced growth.
Next we may ask, what the molecular basis is for Tsanev's theory,
which suggests that neither stimulators nor inhibitors are involved in
growth induced by damage. What is required is a certain amount of sublethal damage (Section IV,A,3). Tsanev (1963, 1966) shows that when
cells are sublethally damaged by mild pressure, there is initially an
increase in cytoplasmic basophilia (Fig. 12). This initial increase in
basophilia does not arise from an increase in cytoplasmic ribonucleoprotein content, but from an altered relationship between RNA and
proteins. In fact the initial increased basophilia is actually accompanied
by a decrease in RNA content (Fig. 12). Later the cytoplasmic RNA
content increases. If the pressure is severe the cells are irreversibly
35
This might be possible since others, who have looked for either stimulators or inhibitors in tissue extracts, have usually found both (SzentGyorgyi et al., 1962; Teir, 1952). This raises the question if there is any
evidence that stimulators may be responsible for the initiation of damageinduced growth.
The literature on the presence of stimulators in cells is enormous
(Abercrombie, 1964; Arey, 1936; Goss, 1964; Loofbourow, 1948; Needham, 1960; Swann, 1958; Washburn, 1960). However the evidence that
stimulators are responsible for damage-induced growth is not compelling.
There has been no serious detailed study of the role of stimulators for
initiating damage-induced growth as there has been by Bullough for
inhibitors. So far the best evidence that stimulators may be involved in
initiating damage-induced growth has been the evidence of Argyris and
Trimble (1964a,b) that the loss of mass and presumably an inhibitor is
not a sufficient cue for initiating growth. But this evidence is strictly
indirect. Recently, Hell (1966) has found that TCA-soluble substances
from epidermal extracts of guinea pig epidermis can stimulate the uptake
of tritiated thymidine in guinea pig epidermal cells in vitro. The isolation
must be done quickly, using serum, and in the cold. The epidermis must
be kept in serum, otherwise activity is lost. This observation is very
important because these substances stimulate epidermal cells to enter
mitosis in the Gi phase of the cell cycle. Such substances could have
general significance for the problem of growth control. The confirmation
and extension of this study may mark the beginning of the definition of
the role of tissue stimulators in the initiation of damage-induced growth.
Thus, the scanty information on the molecular biology of damageinduced growth indicates that both stimulators and inhibitors have been
found in tissues. Each might be (or might not be) significant in the
initiation of damage-induced growth.
Next we may ask, what the molecular basis is for Tsanev's theory,
which suggests that neither stimulators nor inhibitors are involved in
growth induced by damage. What is required is a certain amount of sublethal damage (Section IV,A,3). Tsanev (1963, 1966) shows that when
cells are sublethally damaged by mild pressure, there is initially an
increase in cytoplasmic basophilia (Fig. 12). This initial increase in
basophilia does not arise from an increase in cytoplasmic ribonucleoprotein content, but from an altered relationship between RNA and
proteins. In fact the initial increased basophilia is actually accompanied
by a decrease in RNA content (Fig. 12). Later the cytoplasmic RNA
content increases. If the pressure is severe the cells are irreversibly