The DNA Content of Some Mammalian Cells Measured by Flow Cytometry and its Influence on Radiation Sensitivity

Sontag, W.; Knedlitschek, Gudrun; Weibezahn, Karl-Friedrich; Dertinger, Hermann

doi:10.1080/09553009014551281

Cited by 24 publications

(3 citation statements)

References 34 publications

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“…Because replication initiation in higher eukaryotes is suggested to begin in the micelle cores (see above), the lack of micelle structure in yeast chromosomes is consistent with the observation that higher and lower eukaryotes have different patterns of replication initiation (see review in Gilbert, 1998). (Sontag et al, 1990) 24 0.4-0.9 3-7…”

Section: Relationship Between Size Of Interphase Nucleus and Chromososupporting

confidence: 61%

A Polymer Model for the Structural Organization of Chromatin Loops and Minibands in Interphase Chromosomes

Ostashevsky

1998

MBoC

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A quantitative model of interphase chromosome higher-order structure is presented based on the isochore model of the genome and results obtained in the field of copolymer research. G1 chromosomes are approximated in the model as multiblock copolymers of the 30-nm chromatin fiber, which alternately contain two types of 0.5- to 1-Mbp blocks (R and G minibands) differing in GC content and DNA-bound proteins. A G1 chromosome forms a single-chain string of loop clusters (micelles), with each loop approximately 1-2 Mbp in size. The number of approximately 20 loops per micelle was estimated from the dependence of geometrical versus genomic distances between two points on a G1 chromosome. The greater degree of chromatin extension in R versus G minibands and a difference in the replication time for these minibands (early S phase for R versus late S phase for G) are explained in this model as a result of the location of R minibands at micelle cores and G minibands at loop apices. The estimated number of micelles per nucleus is close to the observed number of replication clusters at the onset of S phase. A relationship between chromosomal and nuclear sizes for several types of higher eukaryotic cells (insects, plants, and mammals) is well described through the micelle structure of interphase chromosomes. For yeast cells, this relationship is described by a linear coil configuration of chromosomes.

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Section: Relationship Between Size Of Interphase Nucleus and Chromososupporting

confidence: 61%

A Polymer Model for the Structural Organization of Chromatin Loops and Minibands in Interphase Chromosomes

Ostashevsky

1998

MBoC

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“…Taking 6.35 Gbp as the G 1 DNA content of the normal human male genome (56), yielded C = 6.5 Gbp for V79 cells in G 1 phase. Estimates in the literature range between 4.3 and 7.6 Gbp for various V79 cell lines (57)(58)(59).…”

Section: Methodsmentioning

confidence: 99%

Higher-Order Structure of Mammalian Chromatin Deduced from Viscoelastometry Data

Ostashevsky

Reichman

Lange

1999

Journal of Biomolecular Structure and Dynamics

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The results of viscoelastometry (VE) for mammalian DNA have been puzzling because they have two orders of magnitude smaller measured viscoelastic relaxation times for mammalian chromosomes than that expected for DNA linear coils of chromosomal size. In an attempt to resolve this discrepancy, we have applied a recent model of G1 chromosome structure (J.Y. Ostashevsky, Mol Biol. Cell 9, 3031-3040, 1998) in which the 30 nm chromatin fiber of each chromosome forms a string of loop clusters (micelles). This model has two parameters: the number of loops per micelle (f) and the average loop size (Mf), which can be estimated independently from VE data. Using our VE data for plateau phase V79 Chinese hamster cells (unirradiated and X-irradiated with doses up to 40 Gy) we show that f approximately 13 , which is close to other estimates made using the model (f ranges from 10-20), and Mf approximately 2 Mbp, which is similar to estimates made from our nucleoid data (1.3 Mbp) and to estimates made in the literature using a variety of techniques (1-3 Mbp).

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“…This work focuses on asynchronized cells since they are more clinically representative and because most in vitro data are available for asynchronized cells. Though the cell morphology, the amount of DNA within the cell nucleus, and the cell radiosensitivity are well known to correlate with the cell cycle phase(Sinclair 1968, Fidorra et al 1981, Sontag et al 1990, Claesson et al 2011, the MCF MKM calculations were performed for an idealized cell that possesses population-mean characteristics (α ref , β ref , R n , r d ). This was the only feasible approach since cell-cycle specific information (i.e.…”

mentioning

confidence: 99%

The Mayo Clinic Florida microdosimetric kinetic model of clonogenic survival: formalism and first benchmark against in vitro and in silico data

2022

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Objective. To develop a new model (Mayo Clinic Florida microdosimetric kinetic model, MCF MKM) capable of accurately describing the in vitro clonogenic survival at low and high linear energy transfer (LET) using single-event microdosimetric spectra in a single target. Methodology. The MCF MKM is based on the ‘post-processing average’ implementation of the non-Poisson microdosimetric kinetic model and includes a novel expression to compute the particle-specific quadratic-dependence of the cell survival with respect to dose (β of the linear-quadratic model). A new methodology to a priori calculate the mean radius of the MCF MKM subnuclear domains is also introduced. Lineal energy spectra were simulated with the Particle and Heavy Ion Transport code System (PHITS) for 1H, 4He, 12C, 20Ne, 40Ar, 56Fe, and 132Xe ions and used in combination with the MCF MKM to calculate the ion-specific LET-dependence of the relative biological effectiveness (RBE) for Chinese hamster lung fibroblasts (V79 cell line) and human salivary gland tumor cells (HSG cell line). The results were compared with in vitro data from the Particle Irradiation Data Ensemble (PIDE) and in silico results of different models. The possibility of performing experiment-specific predictions to explain the scatter in the in vitro RBE data was also investigated. Finally, a sensitivity analysis on the model parameters is also included. Main results. The RBE values predicted with the MCF MKM were found to be in good agreement with the in vitro data for all tested conditions. Though all MCF MKM model parameters were determined a priori, the accuracy of the MCF MKM was found to be comparable or superior to that of other models. The model parameters determined a priori were in good agreement with the ones obtained by fitting all available in vitro data. Significance. The MCF MKM will be considered for implementation in cancer radiotherapy treatment planning with accelerated ions.

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The DNA Content of Some Mammalian Cells Measured by Flow Cytometry and its Influence on Radiation Sensitivity

Cited by 24 publications

References 34 publications

A Polymer Model for the Structural Organization of Chromatin Loops and Minibands in Interphase Chromosomes

A Polymer Model for the Structural Organization of Chromatin Loops and Minibands in Interphase Chromosomes

Higher-Order Structure of Mammalian Chromatin Deduced from Viscoelastometry Data

The Mayo Clinic Florida microdosimetric kinetic model of clonogenic survival: formalism and first benchmark against in vitro and in silico data

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