36
THOMAS S. ARGYRIS
damaged and die. In such cells, the initial RNA degradation is not
followed by its restoration. Tsanev (1963, 1966) speculates that the RNA
that is degraded may be part of the ribonucleoproteins of the microsomal
fraction of the cell. The ribonucleic acid degraded probably includes
messenger RNA and, thus, the polysome structure is disrupted. This, in
turn, stops the synthesis of functional proteins. The breakdown of the
microsomal ribonucleoprotein may be accomplished by the release of the
microsomal RNase. It is speculated that perhaps one of the functional
proteins normally synthesized in a cell is a repressor for the synthesis of
the mitotic proteins. The cessation of the synthesis of this protein occurs
along with the cessation of the rest of protein synthesis. Its loss releases
the inhibition of synthesis of mitotic proteins, and cell division commences. In lethally damaged cells the breakdown of microsomal ribonucleoprotein is irreversible. The RNA breakdown products released from
sublethally or lethally damaged cells probably do not enter other adjacent
cells. If they do, they have no growth-promoting effects on the cells they
enter. The reason that cell division occurs adjacent to an area of necrosis
is that these cells are themselves sublethally damaged. Although the
liberated RNA breakdown products have no growth-promoting effects
they may be responsible for the inflammatory response seen in damage.
Tsanev (1963) has shown that RNA breakdown products can cause the
accumulation of leukocytes—a finding recently confirmed by Walters
and Willoughby (1965).
Each of the theories presented has something to recommend it. The
evidence does not permit a clear choice among them. Indeed it is quite
likely that when enough is known about the molecular basis of damageinduced growth something from each will be incorporated (and discarded)
into a general theory. It is quite possible, for example, that the intracellular events that Tsanev speculates as initiating cell division are correct
and that the chalone of Bullough is the repressor the loss of which
initiates cell division. It is also possible that stimulating substances exist
and have as their locus of attack the release of latent microsomal RNases
that trigger the events leading to cell division. What is needed most now
is an increased experimental effort in each of these general areas.
V. The Relationship of Damage-Induced Growth to
Compensatory Hypertrophy, to Tumor-Induced Growth,
and to Embryonic Development
Since a number of investigators (Bullough, 1965; Goss, 1964) have
recently suggested that the stimulus mechanism is similar for wound
THOMAS S. ARGYRIS
damaged and die. In such cells, the initial RNA degradation is not
followed by its restoration. Tsanev (1963, 1966) speculates that the RNA
that is degraded may be part of the ribonucleoproteins of the microsomal
fraction of the cell. The ribonucleic acid degraded probably includes
messenger RNA and, thus, the polysome structure is disrupted. This, in
turn, stops the synthesis of functional proteins. The breakdown of the
microsomal ribonucleoprotein may be accomplished by the release of the
microsomal RNase. It is speculated that perhaps one of the functional
proteins normally synthesized in a cell is a repressor for the synthesis of
the mitotic proteins. The cessation of the synthesis of this protein occurs
along with the cessation of the rest of protein synthesis. Its loss releases
the inhibition of synthesis of mitotic proteins, and cell division commences. In lethally damaged cells the breakdown of microsomal ribonucleoprotein is irreversible. The RNA breakdown products released from
sublethally or lethally damaged cells probably do not enter other adjacent
cells. If they do, they have no growth-promoting effects on the cells they
enter. The reason that cell division occurs adjacent to an area of necrosis
is that these cells are themselves sublethally damaged. Although the
liberated RNA breakdown products have no growth-promoting effects
they may be responsible for the inflammatory response seen in damage.
Tsanev (1963) has shown that RNA breakdown products can cause the
accumulation of leukocytes—a finding recently confirmed by Walters
and Willoughby (1965).
Each of the theories presented has something to recommend it. The
evidence does not permit a clear choice among them. Indeed it is quite
likely that when enough is known about the molecular basis of damageinduced growth something from each will be incorporated (and discarded)
into a general theory. It is quite possible, for example, that the intracellular events that Tsanev speculates as initiating cell division are correct
and that the chalone of Bullough is the repressor the loss of which
initiates cell division. It is also possible that stimulating substances exist
and have as their locus of attack the release of latent microsomal RNases
that trigger the events leading to cell division. What is needed most now
is an increased experimental effort in each of these general areas.
V. The Relationship of Damage-Induced Growth to
Compensatory Hypertrophy, to Tumor-Induced Growth,
and to Embryonic Development
Since a number of investigators (Bullough, 1965; Goss, 1964) have
recently suggested that the stimulus mechanism is similar for wound