74
Z. SIMON, D. FARCAS, and A. CRISTEA
SIMON:
Our considerations refer to cells in culture of not too high a density. In principle they would also be valid for tissues, although perhaps here other factors,
e.g. the cell volume, could intervene.-Concerning the thymidine kinase,
measurements have indeed been done with the extracted enzyme, to which
labelled substrates have been added in well-known and high concentrations.
However, we would need information on those enzymes in the cells, whose
substrate concentrations (for TMP, TTP) are not known.
KLAMERTH:
Such activities would indeed be difficult to obtain since in the cell precursors
of TMP (for example) could be used also as precursors for RNA-synthesis.How does your model account for the experimental fact that exogenously
given thymidine blocks the progression from G1 to S?
SIMON:
As you know, even TTP inhibits some earlier steps in its synthesis. Our
considerations would nevertheless hold good if C is a precursor of TTP,
rapidly transformable to it, and if a proportionality between the concentrations
of C and TTP exists.
KIEFER:
Cell cycle time is not constant. It would be desirable to introduce stochastic
considerations to take account of the variation of the parameters.-E. coli
does not have a GrS-G z cell cycle, but rather a continuous S-phase. One has
to be careful to use this bacterium for experimental verification.
SIMON:
The test on E. coli is not valid for the whole model. We supposed only linear
volume increase d V/dt = v and that C synthesis is catalyzed by some growthstable protein dC/dt = fP V, decay processes being neglected. Condition (6)
becomes (without implication on eq. 4):
Co = ~ v fP T~ - e
or, as the initial cell volume Vo = v Tc, if the initial precursor quantity is
neglected (Co = 0), one obtains:
TC: cell cycle
9: precursor quantity used
up in DNA synthesis
According to some data on E. coli at various division rates (Tc between 82 and
25 min) (when E. coli double 2 chromosomes per cycle: K. G. LACK, Bact.
Rev. 30, 3, 1966), the product Tc dry mass is approx. constant.-Other tests
were carried out with rapidly dividing mammalian cells (in culture). PI and its
RNA-template were assumed to be unstable (In regenerating liver, thymidine
kinase and thymidylate synthetase really have half-lives of approx. 3 hrs-their
templates also.)-By means of a relation between V o, Tc, T and en, and fP the
first variables are known, we may calculate en. One obtains values lying between 1·10-' and 4.10- 3 mol/I, i.e. not a constant value.
Z. SIMON, D. FARCAS, and A. CRISTEA
SIMON:
Our considerations refer to cells in culture of not too high a density. In principle they would also be valid for tissues, although perhaps here other factors,
e.g. the cell volume, could intervene.-Concerning the thymidine kinase,
measurements have indeed been done with the extracted enzyme, to which
labelled substrates have been added in well-known and high concentrations.
However, we would need information on those enzymes in the cells, whose
substrate concentrations (for TMP, TTP) are not known.
KLAMERTH:
Such activities would indeed be difficult to obtain since in the cell precursors
of TMP (for example) could be used also as precursors for RNA-synthesis.How does your model account for the experimental fact that exogenously
given thymidine blocks the progression from G1 to S?
SIMON:
As you know, even TTP inhibits some earlier steps in its synthesis. Our
considerations would nevertheless hold good if C is a precursor of TTP,
rapidly transformable to it, and if a proportionality between the concentrations
of C and TTP exists.
KIEFER:
Cell cycle time is not constant. It would be desirable to introduce stochastic
considerations to take account of the variation of the parameters.-E. coli
does not have a GrS-G z cell cycle, but rather a continuous S-phase. One has
to be careful to use this bacterium for experimental verification.
SIMON:
The test on E. coli is not valid for the whole model. We supposed only linear
volume increase d V/dt = v and that C synthesis is catalyzed by some growthstable protein dC/dt = fP V, decay processes being neglected. Condition (6)
becomes (without implication on eq. 4):
Co = ~ v fP T~ - e
or, as the initial cell volume Vo = v Tc, if the initial precursor quantity is
neglected (Co = 0), one obtains:
TC: cell cycle
9: precursor quantity used
up in DNA synthesis
According to some data on E. coli at various division rates (Tc between 82 and
25 min) (when E. coli double 2 chromosomes per cycle: K. G. LACK, Bact.
Rev. 30, 3, 1966), the product Tc dry mass is approx. constant.-Other tests
were carried out with rapidly dividing mammalian cells (in culture). PI and its
RNA-template were assumed to be unstable (In regenerating liver, thymidine
kinase and thymidylate synthetase really have half-lives of approx. 3 hrs-their
templates also.)-By means of a relation between V o, Tc, T and en, and fP the
first variables are known, we may calculate en. One obtains values lying between 1·10-' and 4.10- 3 mol/I, i.e. not a constant value.