58
EDWARD C. CANTINO AND JAMES S. LOVETT
sequence, it has become abundantly clear (a) that differential rates of
synthesis of many things occur during the exponential growth of RS
cells; (b) that the RS cell is also an excellent test system for studies of
differential rates of enzyme synthesis ; and (c) that the RS cell, like an
OC cell, simply does not maintain its composition constant during
exponential growth. Rather than dwell further on descriptive details
documented in detail elsewhere, we should like to focus our attention
now, upon the main topic of discussion.
Judging solely from a microscopic point of view, a young RS cell in
the middle of its exponential stage of growth looks like an OC cell at a
corresponding stage in its development ; in so far as gross parameters
which meet the eye are concerned, they are essentially indistinguishable.
But nonetheless, these two cells have embarked upon different pathways
of development (Fig. 2). Therefore, synchronized single generations of
these young RS and OC cells lend themselves beautifully to direct
studies of regulatory mechanisms in morphogenesis. These control
devices begin to operate during exponential growth, before morphological differentiation has become obvious. Thus, it is at this early stage,
when the prospective fates of these two kinds of cells have not yet been
sealed—i.e., they are still pluripotent—that we must consider the
relation between biochemical and morphological differentiation.
The nature of the bicarbonate trigger mechanism for RS differentiation has been investigated for a number of years ; the data have been
reviewed on several occasions (Emerson, 1955; Cantino and Turian,
1959 ; Cantino, 1961a, b). Therefore, we shall simply provide a condensed
recapitulation of the essential biochemical events which we think are
operative, and then use this as a convenient point of departure.
In brief, bicarbonate seems to cause a pronounced shift in the
tricarboxylic acid cycle—specifically, from oxidative decarboxylation of
isocitrate to reductive carboxylation of ketoglutarate (via isocitric
dehydrogenase), removal of the isocitrate by way of isocitritase, and
metabolism of one product, glyoxylate, through glycine-alanine transaminase. A multitude of cellular events (Fig. 5) are known to be
associated, sooner or later, with this bicarbonate trigger mechanism:
alterations in the quality and quantity of RNA, soluble and insoluble
proteins, enzymatic activities, amino-acid and carboxylic acid pools,
carotenoids, soluble polysaccharides, melanin, chitin, and other things
(Cantino, 1961a, b; Cantino and Goldstein, 1961, 1962; Lovett and
Cantino, 1960a, b, c; McCurdy and Cantino, 1960; Cantino and
Horenstein, 1955). Some of the links (Fig. 5) involved in these transformations have been directly demonstrated; other couplings are
inferred from indirect evidence. But, notwithstanding the uncertainty
regarding some anastomoses, all the items labelled in the Figure do
EDWARD C. CANTINO AND JAMES S. LOVETT
sequence, it has become abundantly clear (a) that differential rates of
synthesis of many things occur during the exponential growth of RS
cells; (b) that the RS cell is also an excellent test system for studies of
differential rates of enzyme synthesis ; and (c) that the RS cell, like an
OC cell, simply does not maintain its composition constant during
exponential growth. Rather than dwell further on descriptive details
documented in detail elsewhere, we should like to focus our attention
now, upon the main topic of discussion.
Judging solely from a microscopic point of view, a young RS cell in
the middle of its exponential stage of growth looks like an OC cell at a
corresponding stage in its development ; in so far as gross parameters
which meet the eye are concerned, they are essentially indistinguishable.
But nonetheless, these two cells have embarked upon different pathways
of development (Fig. 2). Therefore, synchronized single generations of
these young RS and OC cells lend themselves beautifully to direct
studies of regulatory mechanisms in morphogenesis. These control
devices begin to operate during exponential growth, before morphological differentiation has become obvious. Thus, it is at this early stage,
when the prospective fates of these two kinds of cells have not yet been
sealed—i.e., they are still pluripotent—that we must consider the
relation between biochemical and morphological differentiation.
The nature of the bicarbonate trigger mechanism for RS differentiation has been investigated for a number of years ; the data have been
reviewed on several occasions (Emerson, 1955; Cantino and Turian,
1959 ; Cantino, 1961a, b). Therefore, we shall simply provide a condensed
recapitulation of the essential biochemical events which we think are
operative, and then use this as a convenient point of departure.
In brief, bicarbonate seems to cause a pronounced shift in the
tricarboxylic acid cycle—specifically, from oxidative decarboxylation of
isocitrate to reductive carboxylation of ketoglutarate (via isocitric
dehydrogenase), removal of the isocitrate by way of isocitritase, and
metabolism of one product, glyoxylate, through glycine-alanine transaminase. A multitude of cellular events (Fig. 5) are known to be
associated, sooner or later, with this bicarbonate trigger mechanism:
alterations in the quality and quantity of RNA, soluble and insoluble
proteins, enzymatic activities, amino-acid and carboxylic acid pools,
carotenoids, soluble polysaccharides, melanin, chitin, and other things
(Cantino, 1961a, b; Cantino and Goldstein, 1961, 1962; Lovett and
Cantino, 1960a, b, c; McCurdy and Cantino, 1960; Cantino and
Horenstein, 1955). Some of the links (Fig. 5) involved in these transformations have been directly demonstrated; other couplings are
inferred from indirect evidence. But, notwithstanding the uncertainty
regarding some anastomoses, all the items labelled in the Figure do