GROWTH INDUCED BY DAMAGE
31
stimulate hair growth. The observation of Bullough and Laurence (1960a)
that a small cut made on one side of an ear induces mitotic activity, not
only in the adjacent epidermis, but also in the epidermis on the opposite
side of the ear, in which presumably no damage has been inflicted, is
also not easily explainable by Tsanev's hypothesis that direct sublethal
damage is required for cell proliferation. The fact that damage to one
kidney results in mitotic activity in the cortex of the contralateral kidney
and that, furthermore, this stimulation does not result from the attendant
loss of kidney mass, suggests that growth-promoting substances can be
released from damaged cells (Argyris and Trimble, 1964b). Finally, the
demonstration that crushing a nerve leads to an intense mitotic activity
of the connective tissue of the regenerating nerve, which is some distance
from the point of damage, also argues for the release of stimulating
substances in wound healing (Abercrombie and Santler, 1957).
B. The Molecular Basis for the Mechanism of Damage-Induced Growth
Earlier we have presented evidence that suggests that the local loss of
tissue mass, and thus the accompanying loss of inhibitor (Bullough,
1965), may not be the initiating stimulus of damage-induced growth. But
this does not mean that inhibitors are not critical in controlling proliferation, since it may be that wounds release substances, the function of
which is to inactivate the inhibitors, which, in turn, trigger mitotic
activity. Therefore the role of inhibitors in damage-induced growth is a
subject that stands independently from that of the role of the loss of
tissue mass.
Bullough and his colleagues (Bullough and Laurence, 1964; Bullough
et al., 1964) have isolated a substance from the epidermis which they
have demonstrated can inhibit the mitotic activity of epidermal cells
in vitro and in vivo. They call this substance an epidermal chalone. The
function of this epidermal chalone is to control the level of the mitotic
activity of the epidermis. Largely on the basis of their evidence for a
chalone in mouse ear epidermis, Bullough has suggested that the mitotic
activity of all tissues is controlled by chalon.es (Bullough, 1962, 1964,
1965). Since these notions have been repeatedly discussed by Bullough
(1962, 1964, 1965) and others (Goss, 1964), no further detailed discussion is necessary.
The epidermal chalone, to act, must be combined with adrenaline as a
cofactor (Bullough and Laurence, 1964; Bullough et al., 1964). The
chalone is a protein and perhaps a glycoprotein; although at the moment
the evidence is not yet conclusive (Bullough, 1966). Bullough has
31
stimulate hair growth. The observation of Bullough and Laurence (1960a)
that a small cut made on one side of an ear induces mitotic activity, not
only in the adjacent epidermis, but also in the epidermis on the opposite
side of the ear, in which presumably no damage has been inflicted, is
also not easily explainable by Tsanev's hypothesis that direct sublethal
damage is required for cell proliferation. The fact that damage to one
kidney results in mitotic activity in the cortex of the contralateral kidney
and that, furthermore, this stimulation does not result from the attendant
loss of kidney mass, suggests that growth-promoting substances can be
released from damaged cells (Argyris and Trimble, 1964b). Finally, the
demonstration that crushing a nerve leads to an intense mitotic activity
of the connective tissue of the regenerating nerve, which is some distance
from the point of damage, also argues for the release of stimulating
substances in wound healing (Abercrombie and Santler, 1957).
B. The Molecular Basis for the Mechanism of Damage-Induced Growth
Earlier we have presented evidence that suggests that the local loss of
tissue mass, and thus the accompanying loss of inhibitor (Bullough,
1965), may not be the initiating stimulus of damage-induced growth. But
this does not mean that inhibitors are not critical in controlling proliferation, since it may be that wounds release substances, the function of
which is to inactivate the inhibitors, which, in turn, trigger mitotic
activity. Therefore the role of inhibitors in damage-induced growth is a
subject that stands independently from that of the role of the loss of
tissue mass.
Bullough and his colleagues (Bullough and Laurence, 1964; Bullough
et al., 1964) have isolated a substance from the epidermis which they
have demonstrated can inhibit the mitotic activity of epidermal cells
in vitro and in vivo. They call this substance an epidermal chalone. The
function of this epidermal chalone is to control the level of the mitotic
activity of the epidermis. Largely on the basis of their evidence for a
chalone in mouse ear epidermis, Bullough has suggested that the mitotic
activity of all tissues is controlled by chalon.es (Bullough, 1962, 1964,
1965). Since these notions have been repeatedly discussed by Bullough
(1962, 1964, 1965) and others (Goss, 1964), no further detailed discussion is necessary.
The epidermal chalone, to act, must be combined with adrenaline as a
cofactor (Bullough and Laurence, 1964; Bullough et al., 1964). The
chalone is a protein and perhaps a glycoprotein; although at the moment
the evidence is not yet conclusive (Bullough, 1966). Bullough has