GROWTH INDUCED BY DAMAGE
33
presented evidence that the epidermal chalone is quite specific in inhibiting mitosis in vitro. Substances have been extracted from a wide variety
of tissues, with methods as nearly as possible alike to those that have
been used to extract the epidermal chalone (Bullough and Laurence,
1964). Therefore, such extracts should include the organ-specific chalones.
It is clear from Table IV that except possibly for the kidney extracts
none have much inhibiting effect on epidermal mitosis in vitro. The
converse experiment of determining the effect of the epidermal chalone
on the mitotic activity of other tissues in vitro has also been done. Table
V shows that there is some inhibition by the epidermal chalone of the
mitotic activity of other tissues such as the cornea and anterior esophagus. But all these tissues are epidermal derivatives (Bullough and
Laurence, 1964). Thus the evidence is clear that an inhibitor or chalone
can be extracted from the epidermis which can inhibit epidermal mitotic
activity and which, in vitro, has considerable specificity. One major
problem remains, and that is that so far the principal inhibitory effect of
the epidermal chalone on epidermal cell mitotic activity is largely in
the G 2 phase or antiphase of the cell cycle (Bullough, 1964). As Bullough
(1964) himself clearly points out, the major control point in the life
cycle of cells which is probably the most crucial in the control of cell
division is in the G x phase of the cell cycle. It is our opinion that the
determination of the ability of chalones to inhibit cells in G x from
entering mitosis is one of the most important points which must be
established for the chalones to have general significance in the study of
growth control, and it is certainly one of the exciting future problems in
this field.
Balazs and Holmgren (1950) have also isolated a water-soluble inhibitor from granulation tissue of wounds that inhibits mitotic activity of
fibroblasts in vitro. The greatest inhibitory effect is from extracts of
granulation tissue from 6-9 days after wounding. It is at this time that
granulation tissue shows its most intense metachromasia according to
these investigators (Balazs and Holmgren, 1950). Because of this, Balazs
and Holmgren (1950) have suggested their inhibitor might be a mucopolysaccharide or mucoprotein. In this it may share something in common
with the epidermal chalone of Bullough, which is also water-soluble and
may be a mucoprotein (Bullough, 1966). Balazs and Holmgren (1950)
also have looked for stimulating substances in wound tissue and have
reported that a saline extract from granulation tissue stimulates the
mitotic activity of fibroblasts in vitro. It would be important to determine
if similar extraction procedures of the epidermis can yield stimulators.
33
presented evidence that the epidermal chalone is quite specific in inhibiting mitosis in vitro. Substances have been extracted from a wide variety
of tissues, with methods as nearly as possible alike to those that have
been used to extract the epidermal chalone (Bullough and Laurence,
1964). Therefore, such extracts should include the organ-specific chalones.
It is clear from Table IV that except possibly for the kidney extracts
none have much inhibiting effect on epidermal mitosis in vitro. The
converse experiment of determining the effect of the epidermal chalone
on the mitotic activity of other tissues in vitro has also been done. Table
V shows that there is some inhibition by the epidermal chalone of the
mitotic activity of other tissues such as the cornea and anterior esophagus. But all these tissues are epidermal derivatives (Bullough and
Laurence, 1964). Thus the evidence is clear that an inhibitor or chalone
can be extracted from the epidermis which can inhibit epidermal mitotic
activity and which, in vitro, has considerable specificity. One major
problem remains, and that is that so far the principal inhibitory effect of
the epidermal chalone on epidermal cell mitotic activity is largely in
the G 2 phase or antiphase of the cell cycle (Bullough, 1964). As Bullough
(1964) himself clearly points out, the major control point in the life
cycle of cells which is probably the most crucial in the control of cell
division is in the G x phase of the cell cycle. It is our opinion that the
determination of the ability of chalones to inhibit cells in G x from
entering mitosis is one of the most important points which must be
established for the chalones to have general significance in the study of
growth control, and it is certainly one of the exciting future problems in
this field.
Balazs and Holmgren (1950) have also isolated a water-soluble inhibitor from granulation tissue of wounds that inhibits mitotic activity of
fibroblasts in vitro. The greatest inhibitory effect is from extracts of
granulation tissue from 6-9 days after wounding. It is at this time that
granulation tissue shows its most intense metachromasia according to
these investigators (Balazs and Holmgren, 1950). Because of this, Balazs
and Holmgren (1950) have suggested their inhibitor might be a mucopolysaccharide or mucoprotein. In this it may share something in common
with the epidermal chalone of Bullough, which is also water-soluble and
may be a mucoprotein (Bullough, 1966). Balazs and Holmgren (1950)
also have looked for stimulating substances in wound tissue and have
reported that a saline extract from granulation tissue stimulates the
mitotic activity of fibroblasts in vitro. It would be important to determine
if similar extraction procedures of the epidermis can yield stimulators.