260
J O H N P A U L
which would effectively result in a lowering of intracellular concentrations of these substances. Observations by Whitfield and Rixon (1961)
would support an explanation of this kind.
The actual mechanism of the Crabtree effect is obscure but it is not
unlikely that it is due to competition between different pathways for a
common metabolite, such as ADP, as will be discussed later.
3. Effect of Oxygen Tension
Analogous to the Crabtree effect is the Pasteur effect. When the
oxygen tension in the medium is lowered, glucose utilization has been
found by some workers (Danes et al., 1963; Suschny et al., 1958) to
increase. On the other hand W u (1959) failed to demonstrate a Pasteur
effect in HeLa cells in relation to exogenous carbohydrate although he
observed a Pasteur effect in relation to endogenous carbohydrate. It is
worth noting that Wu's observations were made over a shorter time
than the others referred to and may therefore represent a more genuine
test of the Pasteur phenomenon.
The Pasteur effect will be discussed later in relation to regulating
mechanisms.
Most cells exhibit a definite optimum oxygen tension for growth and
survival. As has already been mentioned some cells may grow for some
time at very low oxygen tension (Burrows, 1921, 1924; Dales, 1960;
Gifford, 1960; H. Harris, 1956; Laser, 1933; Medawar, 1947; Meier,
1931; Warburg, 1930; Warburg and Kubowitz, 1927) but most
observations on cell strains indicate that they grow very slowly, if at
all, at zero oxygen tension and that the growth rate rapidly diminishes
as zero tension is approached (Dales, 1960; Gifford, 1960; Fisher,
1960). O n the other hand, and perhaps surprisingly, it has repeatedly
been observed that high oxygen tensions are even more rapidly lethal
(Brosemer and Rutter, 1961; Cooper, Burt and Wilson, 1958; Gifford,
1960; Rueckert and Mueller, 1960). When cells are grown in a medium
equilibrated with 95°/o oxygen they at first grow and respire rapidly
and also exhibit a high glycolytic rate (Brosemer and Rutter, 1961;
Rueckert and Mueller, 1960). They then die very quickly. The reason
for this oxygen toxicity is not known, but Lieberman and Ove (1958a)
have suggested that one reason may be the accumulation of peroxides,
and they have claimed better results in a medium to which some
catalase has been added.
The oxygen tension may be of importance in the handling of cell
cultures. Thus Fischer (1928) and Osgood and Krippaehne (1955)
maintained that different cell-types grow best at specific oxygen
tensions while Cooper, Burt and Wilson (1958) have emphasized the
important role of oxygen tension in continuous suspension cultures. The
J O H N P A U L
which would effectively result in a lowering of intracellular concentrations of these substances. Observations by Whitfield and Rixon (1961)
would support an explanation of this kind.
The actual mechanism of the Crabtree effect is obscure but it is not
unlikely that it is due to competition between different pathways for a
common metabolite, such as ADP, as will be discussed later.
3. Effect of Oxygen Tension
Analogous to the Crabtree effect is the Pasteur effect. When the
oxygen tension in the medium is lowered, glucose utilization has been
found by some workers (Danes et al., 1963; Suschny et al., 1958) to
increase. On the other hand W u (1959) failed to demonstrate a Pasteur
effect in HeLa cells in relation to exogenous carbohydrate although he
observed a Pasteur effect in relation to endogenous carbohydrate. It is
worth noting that Wu's observations were made over a shorter time
than the others referred to and may therefore represent a more genuine
test of the Pasteur phenomenon.
The Pasteur effect will be discussed later in relation to regulating
mechanisms.
Most cells exhibit a definite optimum oxygen tension for growth and
survival. As has already been mentioned some cells may grow for some
time at very low oxygen tension (Burrows, 1921, 1924; Dales, 1960;
Gifford, 1960; H. Harris, 1956; Laser, 1933; Medawar, 1947; Meier,
1931; Warburg, 1930; Warburg and Kubowitz, 1927) but most
observations on cell strains indicate that they grow very slowly, if at
all, at zero oxygen tension and that the growth rate rapidly diminishes
as zero tension is approached (Dales, 1960; Gifford, 1960; Fisher,
1960). O n the other hand, and perhaps surprisingly, it has repeatedly
been observed that high oxygen tensions are even more rapidly lethal
(Brosemer and Rutter, 1961; Cooper, Burt and Wilson, 1958; Gifford,
1960; Rueckert and Mueller, 1960). When cells are grown in a medium
equilibrated with 95°/o oxygen they at first grow and respire rapidly
and also exhibit a high glycolytic rate (Brosemer and Rutter, 1961;
Rueckert and Mueller, 1960). They then die very quickly. The reason
for this oxygen toxicity is not known, but Lieberman and Ove (1958a)
have suggested that one reason may be the accumulation of peroxides,
and they have claimed better results in a medium to which some
catalase has been added.
The oxygen tension may be of importance in the handling of cell
cultures. Thus Fischer (1928) and Osgood and Krippaehne (1955)
maintained that different cell-types grow best at specific oxygen
tensions while Cooper, Burt and Wilson (1958) have emphasized the
important role of oxygen tension in continuous suspension cultures. The