294
H A R R Y E A G L E A N D L E O N L E V I N T O W
active amines (Schindler, Day and Fischer, 1959), such examples are
comparatively rare, and the factors leading to the persistence of function in these instances are not apparent.
Equally obscure are the reasons for the usual disappearance of
specialized structure and function in the course of the establishment of
a serial line from the original tissue explant. It is conceivable that
rapid growth in vitro is incompatible for most cells with the maintenance of specialized cell function, or in fact that this relatively rapid
growth rate is possible only for the "dedifferentiated" cells. In at least
one cell, however, this is not the case. Intestinal epithelial cells in the
intact rat have been shown to have a turnover time of 24-29 h, of
the same order of magnitude as that of serially propagated cells in
vitro (Stevens-Hooper, 1961). Although the cell "turnover" rate o f
most other tissues is considerably slower, this finding does indicate
that for certain cells in the living animal a high growth rate is not
incompatible with a high degree of functional and morphological
differentiation.
The kinetics of the disappearance of functional characteristics
(Lieberman and Ove, 1958) as well as other observations (cf. Levintow
and Eagle, 1961) suggest that most of the cell lines which can be
maintained in serial culture are "dedifferentiated". T w o general mechanisms for this phenomenon have been proposed: (1) failure of the
functioning cells to multiply, with consequent selection of undifferentiated cells, and (2) the actual loss of function on cultivation. Evidence
has been obtained in favor of both these mechanisms, and it seems
possible that either may play a role, depending on the tissue and the
experimental conditions.
If "dedifferentiation" is in fact the operative mechanism, there is no
present explanation in chemical terms of the disappearance of the
specialized function. One may speculate whether the maintenance of
specialized function requires the presence of one or more substances
which are produced and retained by the cells in organized tissues
in vivo but (1) which are dissipated and therefore unavailable when
such cells are dispersed under the usual conditions of culture in vitro
(cf. p. 285), or (2) which the cells cannot make under conditions of
rapid growth. Alternatively, the substance(s) necessary for function
may be provided in vivo by other tissues.
B. M E T A B O L I C C O N T R O L S IN B I O S Y N T H E S I S
As described in the foregoing section, the rapid growth rate of cultured cells distinguishes them from the great majority of cells in vivo.
It seems clear that the in vitro cell has in some measure escaped from
H A R R Y E A G L E A N D L E O N L E V I N T O W
active amines (Schindler, Day and Fischer, 1959), such examples are
comparatively rare, and the factors leading to the persistence of function in these instances are not apparent.
Equally obscure are the reasons for the usual disappearance of
specialized structure and function in the course of the establishment of
a serial line from the original tissue explant. It is conceivable that
rapid growth in vitro is incompatible for most cells with the maintenance of specialized cell function, or in fact that this relatively rapid
growth rate is possible only for the "dedifferentiated" cells. In at least
one cell, however, this is not the case. Intestinal epithelial cells in the
intact rat have been shown to have a turnover time of 24-29 h, of
the same order of magnitude as that of serially propagated cells in
vitro (Stevens-Hooper, 1961). Although the cell "turnover" rate o f
most other tissues is considerably slower, this finding does indicate
that for certain cells in the living animal a high growth rate is not
incompatible with a high degree of functional and morphological
differentiation.
The kinetics of the disappearance of functional characteristics
(Lieberman and Ove, 1958) as well as other observations (cf. Levintow
and Eagle, 1961) suggest that most of the cell lines which can be
maintained in serial culture are "dedifferentiated". T w o general mechanisms for this phenomenon have been proposed: (1) failure of the
functioning cells to multiply, with consequent selection of undifferentiated cells, and (2) the actual loss of function on cultivation. Evidence
has been obtained in favor of both these mechanisms, and it seems
possible that either may play a role, depending on the tissue and the
experimental conditions.
If "dedifferentiation" is in fact the operative mechanism, there is no
present explanation in chemical terms of the disappearance of the
specialized function. One may speculate whether the maintenance of
specialized function requires the presence of one or more substances
which are produced and retained by the cells in organized tissues
in vivo but (1) which are dissipated and therefore unavailable when
such cells are dispersed under the usual conditions of culture in vitro
(cf. p. 285), or (2) which the cells cannot make under conditions of
rapid growth. Alternatively, the substance(s) necessary for function
may be provided in vivo by other tissues.
B. M E T A B O L I C C O N T R O L S IN B I O S Y N T H E S I S
As described in the foregoing section, the rapid growth rate of cultured cells distinguishes them from the great majority of cells in vivo.
It seems clear that the in vitro cell has in some measure escaped from