284
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
Cells are able to synthesize the purine and pyrimidine moieties of
nucleic acid, as well as the ribose and deoxyribose, de novo from glucose,
glutamine and other constituents of the minimal medium. Lipids are
generally not required by serially cultured cells, and usually the lipid
content of such cells is low. Under special conditions, however, cells
can accumulate large amounts of lipids of various sorts. N o nutritional
requirement for a steroid or protein hormone has been demonstrated,
nor, for that matter, any necessary role of these compounds in the
biological economy of these cells.
E. P O S S I B L E A R T I F A C T S
It is not yet clear to what degree the nutritional requirements
indicated above have been affected by the fact that many serially
propagated cell lines are contaminated with pleuropneumonia-like
organisms (PPLO), as a consequence of the regular use of antibiotics
in the culture medium. Although it seems probable that the requirements indicated above are in fact those of the cell, rather than artifacts
imposed by such contamination, it must nevertheless be pointed out
that in at least one instance that contamination has had a demonstrable effect on cellular metabolism. At high population densities
mammalian cells can synthesize many viruses without exogenous amino
acids, since there are ample amounts in the intracellular pool under
these conditions. In the biosynthesis of adenovirus, however, exogenous
arginine was observed to be necessary. That requirement has now been
shown to be due to the catabolic effect of the PPLO contaminant on
the arginine, and disappeared when PPLO was suppressed by treatment
with kanamycin (Rouse and Bonifas, 1962; Schlesinger, personal
communication).
F. P O P U L A T I O N - D E P E N D E N T R E Q U I R E M E N T S
A N D T H E I R B E A R I N G O N T H E Q U E S T I O N OF
C E L L U L A R D I F F E R E N T I A T I O N A N D F U N C T I O N
The profound metabolic differences between dispersed cell cultures
and the original tissue, reflected in their widely varying growth rates,
their varying nutritional requirements and metabolic activities, and
in particular, in the disappearance of organ-specific functions, have
not yet been adequately explained. These differences may, in fact,
prove to be interrelated. One obvious factor of possible relevance is
the large difference between the cellular population densities in vivo
and in vitro. Even a heavy cell culture usually contains no more than
500,000 cells/ml, while in organized tissue the population density is
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
Cells are able to synthesize the purine and pyrimidine moieties of
nucleic acid, as well as the ribose and deoxyribose, de novo from glucose,
glutamine and other constituents of the minimal medium. Lipids are
generally not required by serially cultured cells, and usually the lipid
content of such cells is low. Under special conditions, however, cells
can accumulate large amounts of lipids of various sorts. N o nutritional
requirement for a steroid or protein hormone has been demonstrated,
nor, for that matter, any necessary role of these compounds in the
biological economy of these cells.
E. P O S S I B L E A R T I F A C T S
It is not yet clear to what degree the nutritional requirements
indicated above have been affected by the fact that many serially
propagated cell lines are contaminated with pleuropneumonia-like
organisms (PPLO), as a consequence of the regular use of antibiotics
in the culture medium. Although it seems probable that the requirements indicated above are in fact those of the cell, rather than artifacts
imposed by such contamination, it must nevertheless be pointed out
that in at least one instance that contamination has had a demonstrable effect on cellular metabolism. At high population densities
mammalian cells can synthesize many viruses without exogenous amino
acids, since there are ample amounts in the intracellular pool under
these conditions. In the biosynthesis of adenovirus, however, exogenous
arginine was observed to be necessary. That requirement has now been
shown to be due to the catabolic effect of the PPLO contaminant on
the arginine, and disappeared when PPLO was suppressed by treatment
with kanamycin (Rouse and Bonifas, 1962; Schlesinger, personal
communication).
F. P O P U L A T I O N - D E P E N D E N T R E Q U I R E M E N T S
A N D T H E I R B E A R I N G O N T H E Q U E S T I O N OF
C E L L U L A R D I F F E R E N T I A T I O N A N D F U N C T I O N
The profound metabolic differences between dispersed cell cultures
and the original tissue, reflected in their widely varying growth rates,
their varying nutritional requirements and metabolic activities, and
in particular, in the disappearance of organ-specific functions, have
not yet been adequately explained. These differences may, in fact,
prove to be interrelated. One obvious factor of possible relevance is
the large difference between the cellular population densities in vivo
and in vitro. Even a heavy cell culture usually contains no more than
500,000 cells/ml, while in organized tissue the population density is
