Cell Population Kinetics: A Modified Interpretation of the Graph of Labeled Mitoses

Hamilton, A. Ian

doi:10.1126/science.164.3882.952

Cited by 21 publications

(3 citation statements)

References 11 publications

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“…Let us stress the fact that the second anomaly (two smaller waves at the top of the first wave of labelled mitoses), though not always described, is evident in some other published PLM curves (Atlas & Bond, 1965;Downes et al, 1966;Lipkin, Sherlock & Bell, 1962;Odartchenko et al, 1963). Hamilton (1969) considered that the depressions in the curves are manifestations of interruption of DNA synthesis midway through S phase. This interruption could relate to the necessity of duplicating and assembling the protein framework of the chromosome as well as its DNA.…”

Section: Interpretation Of the Curve Of Labelled Mitosesmentioning

confidence: 99%

Activity of Tubulosine on the Kinetics of Root Meristem Cell Population

Pareyre¹,

Deysson²

1975

Cell Proliferation

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The action of tubulosine on the mitotic cycle was studied using continuous labelling with tritiated thymidine. This alkaloid provokes a lengthening of the G1 and S phases and a blocking of G2 is totally reversible when the treatment is followed by recovery in normal medium. At a dose of tubulosine which induces a reversible mitostasis in the shortest possible time the lengthening of the phases of the cell cycle was estimated by three different techniques: labelled mitoses for the determination of G2; labelling intensity for the determination of S; binucleate cells for the determination of T, and an original technique using labelling index of binucleate cells for the determination of G1. The limits of the technique of labelled mitosis together with the interest of the technique aiming at the direct determination of G1 in the case of a perturbed cycle are then discussed.

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Section: Interpretation Of the Curve Of Labelled Mitosesmentioning

confidence: 99%

Activity of Tubulosine on the Kinetics of Root Meristem Cell Population

Pareyre¹,

Deysson²

1975

Cell Proliferation

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“…Varying rates of DNA synthesis during the S phase of the cell cycle have been noted by several authors (Kasten & Strasser, 1966;Hamilton, 1969;Hamlin & Pardee, 1978;Benei, Rotreklova & VelEovsky, 1978). Hamilton (1969) arrived at the conclusion that there might be an interruption of DNA synthesis midway through S phase, from analysis of labelled mitosis curves. The data referred to rat intestinal mucosa studied in vivo.…”

Section: Discussionmentioning

confidence: 77%

Decreased Sensitivity to Hydroxyurea and to [³H]Thymidine Suicide In the Middle of the S Phase

1981

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Pluripotent haemopoietic stem cells (CFUs) move synchronously through the cell cycle in hydroxyurea‐treated mice in a cohort 1–2 hr broad. Ten to fifteen hours after hydroxyurea they pass through S phase. DNA synthesis appears to be depressed 5–10 times when the cells are in the middle part of the S phase but does not seem to be completely interrupted. High concentrations of [3H]thymidine must be used for ‘suicide’ in order to achieve lethality for the cells with depressed DNA synthesis. At the time when DNA synthesis is depressed, the sensitivity of the cells to hydroxyurea also decreases. This may lead to a significant underestimation of the S phase fraction by the hydroxyurea method, because CFUs with low DNA synthesis rate are resistant to hydroxyurea although being in S phase.

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“…The fact that important, potentially restrictive biochemical events do occur in both the S and G, phases has been indicated both implicitly and explicitly by a variety of investigators (Bostock, Prescott & Kirkpatrick, 197 1 ;Bradbury et al, 1973;Choe & Rose, 1973;Cooper, 1979;Drewinko & Barlogie. 1984;Epifanova & Terskikh, 1969;Flamm, Bernhein & Banbaker, 1971;Gelfant, 1977;Hamilton, 1969;Kapp & Painter, 1977;Karn el al., 1974;Melero, 1979;Mitchison, 1977;Ozer, 1978;Rao & Johnson, 1970;Till, Whitmore & Gulyas, 1963;Tobey, Petersen & Anderson, 1971).…”

Section: Discussionmentioning

confidence: 99%

Cultured Human Tumour Cells May Be Arrested In All Stages of the Cycle During Stationary Phase: Demonstration of Quiescent Cells In G₁, S and G₂ Phase

et al. 1984

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Six human colon carcinoma cell lines were induced to enter stationary phase of growth by nutrient deprivation and cell crowding. Growth kinetics parameters (cell number, flow cytometric analysis of D N A distribution, and labelling and mitotic indices) were measured sequentially for all lines during the various stages of in vitro growth. Our results demonstrated that a substantial fraction of cells (9-18%) were located in G , phase when they changed from an exponential to a stationary mode of growth. Moreover, a large number of cells in stationary phase of growth had an S-phase D N A content, as determined by flow cytometry, but failed to incorporate radioactive D N A precursors (up to 15-fold difference). To substantiate these findings, cells in stationary phase of growth were induced to enter exponential growth by re-seeding in fresh medium at a lower density. Subsequently observed changes in DNA-compartment distribution, and in labelling and mitotic indices were those expected from cells that had been arrested at different stages of the cycle during their previous stationary phase. Thus, the non-proliferating quiescent state (Q), traditionally located 'somewhere' in G, phase, appears to be composed also of cells that can be arrested at other stages of the cycle (Q, and QG). Although the proportion of such cells is rather small, their contribution to the growth kinetics behaviour of human in vivo tumours will become apparent following 'recruiting' or 'synchronizing' clinical manoeuvres and will prevent the formation of a clear-cut wave of synchronized cells.Permanently cultured human cancer cells are a convenient and economic in virro model for evaluating the spectrum of behaviours of clinical tumours. However, one of the major drawbacks of tissue culture experiments resides in the difficulty of extrapolating information from i,7 vifro exponentially growing cells to the expected responses of tumour cells in uivo where large fractions of the population may be in a quiescent state. This is especially important in the case of human solid tumours where low labelling index values suggest the presence of only a small proportion of proliferating cells (low growth fraction). Some investigators have proposed the use of stationary-phase cultures as adequate in uifro models

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Cell Population Kinetics: A Modified Interpretation of the Graph of Labeled Mitoses

Cited by 21 publications

References 11 publications

Activity of Tubulosine on the Kinetics of Root Meristem Cell Population

Activity of Tubulosine on the Kinetics of Root Meristem Cell Population

Decreased Sensitivity to Hydroxyurea and to [³H]Thymidine Suicide In the Middle of the S Phase

Cultured Human Tumour Cells May Be Arrested In All Stages of the Cycle During Stationary Phase: Demonstration of Quiescent Cells In G₁, S and G₂ Phase

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Cell Population Kinetics: A Modified Interpretation of the Graph of Labeled Mitoses

Cited by 21 publications

References 11 publications

Activity of Tubulosine on the Kinetics of Root Meristem Cell Population

Activity of Tubulosine on the Kinetics of Root Meristem Cell Population

Decreased Sensitivity to Hydroxyurea and to [3H]Thymidine Suicide In the Middle of the S Phase

Cultured Human Tumour Cells May Be Arrested In All Stages of the Cycle During Stationary Phase: Demonstration of Quiescent Cells In G1, S and G2 Phase

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Decreased Sensitivity to Hydroxyurea and to [³H]Thymidine Suicide In the Middle of the S Phase

Cultured Human Tumour Cells May Be Arrested In All Stages of the Cycle During Stationary Phase: Demonstration of Quiescent Cells In G₁, S and G₂ Phase