20
THOMAS S. ARGYRIS
containing epidermis, dermis, and cartilage was put cartilage upside
down on the epidermis of an intact ear, and an area of 3 mm square
composed of epidermis and superficial dermis was removed from this
piece with a dental drill. The intact ear was then removed, sectioned,
and the epidermal mitotic activity determined in the area that underlay
the piece of ear drilled. It was reasoned that if pressure from burring
causes an increase in mitotic activity, then the epidermis in the intact
ear should show an increase in mitotic activity. No such increase in
mitotic activity was observed. It has been, therefore, concluded that the
mitotic activity in the epidermis on the side opposite the wound, in the
original experiment, is not caused by damage from the burring.
Although this conclusion seems to us a reasonable one, there are certain
points about this control experiment that open it to question. In the
experiment in which the split skin has been burred, the epidermis of the
intact ear beneath the split skin, the response of which we are interested
in, faces the burring with its cornified surface. In the original experiment,
the epidermis faces the burring with its undersurface, which is lined by
the basal cells. It is possible that the lack of response of the basal cell
layer in the "control" experiment owes to the fact that it secures some
protection from the cornified layer. Perhaps of greater concern is the
fact that in the original experiment the side of the ear burred is in
physiological continuity with the side being tested for its response tb the
burring. In the control experiment, a dead sheet of skin that has no
vascular connections with the target epidermis is placed on top of the
target epidermis. Whether or not these differences in experimental design
are critical cannot be definitely decided. Recently, Tsanev (1963) has
shown that if as little as 15 kg/cm
2 of pressure is applied to the epidermis
in vivo it will result in a change in the degree of epidermal ribonucleic
acid (RNA) polymerization, which he associates with the induction of
mitotic activity in the epidermis. But, as much as 1000 kg/cm
2 of pressure
on the same epidermis in vitro has no effect on the RNA polymerization
of the epidermal cells. This experiment suggests that the activation of
some key molecular processes in the epidermis may be easier in vivo than
in vitro. These objections do not by themselves invalidate the experiments
of Bullough and Laurence (1960a), but they are sufficiently important
that experiments should be devised that rule them out. Also, they suggest
the need for using other approaches to determine if the loss of mass is
the stimulus for the initiation of growth in damage. To meet this need we
have devised a technique by which tumor tissue is inoculated into an
organ and the tumor is allowed to invade the organ. Tumor invasion
THOMAS S. ARGYRIS
containing epidermis, dermis, and cartilage was put cartilage upside
down on the epidermis of an intact ear, and an area of 3 mm square
composed of epidermis and superficial dermis was removed from this
piece with a dental drill. The intact ear was then removed, sectioned,
and the epidermal mitotic activity determined in the area that underlay
the piece of ear drilled. It was reasoned that if pressure from burring
causes an increase in mitotic activity, then the epidermis in the intact
ear should show an increase in mitotic activity. No such increase in
mitotic activity was observed. It has been, therefore, concluded that the
mitotic activity in the epidermis on the side opposite the wound, in the
original experiment, is not caused by damage from the burring.
Although this conclusion seems to us a reasonable one, there are certain
points about this control experiment that open it to question. In the
experiment in which the split skin has been burred, the epidermis of the
intact ear beneath the split skin, the response of which we are interested
in, faces the burring with its cornified surface. In the original experiment,
the epidermis faces the burring with its undersurface, which is lined by
the basal cells. It is possible that the lack of response of the basal cell
layer in the "control" experiment owes to the fact that it secures some
protection from the cornified layer. Perhaps of greater concern is the
fact that in the original experiment the side of the ear burred is in
physiological continuity with the side being tested for its response tb the
burring. In the control experiment, a dead sheet of skin that has no
vascular connections with the target epidermis is placed on top of the
target epidermis. Whether or not these differences in experimental design
are critical cannot be definitely decided. Recently, Tsanev (1963) has
shown that if as little as 15 kg/cm
2 of pressure is applied to the epidermis
in vivo it will result in a change in the degree of epidermal ribonucleic
acid (RNA) polymerization, which he associates with the induction of
mitotic activity in the epidermis. But, as much as 1000 kg/cm
2 of pressure
on the same epidermis in vitro has no effect on the RNA polymerization
of the epidermal cells. This experiment suggests that the activation of
some key molecular processes in the epidermis may be easier in vivo than
in vitro. These objections do not by themselves invalidate the experiments
of Bullough and Laurence (1960a), but they are sufficiently important
that experiments should be devised that rule them out. Also, they suggest
the need for using other approaches to determine if the loss of mass is
the stimulus for the initiation of growth in damage. To meet this need we
have devised a technique by which tumor tissue is inoculated into an
organ and the tumor is allowed to invade the organ. Tumor invasion