Inhibition of DNA synthesis in synchronized Chinese hamster cells treated in G1 with cycloheximide

Schneiderman, Marvin A.; Dewey, William C.; Highfield, D.P.

doi:10.1016/0014-4827(71)90630-6

Cited by 186 publications

(66 citation statements)

References 29 publications

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“…Instead, the rate of transit was severely diminished as the rate of protein synthesis decreased; it became 0 (e.g., T = ca) when f = 0.38. Using F = 0.38, we fitted the data with the line shown, which gives the half-life of R [equal to (1/ (12). Thus, the model based on accumulation of a labile protein and our data are quantitatively consistent.…”

Section: Discussionsupporting

confidence: 64%

Synthesis of labile, serum-dependent protein in early G ₁ controls animal cell growth

Rossow

Riddle

Pardee

1979

Proc. Natl. Acad. Sci. U.S.A.

244

117

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We present a model to account for several major observations on growth control of animal cells in culture. This model is tested by means of kinetic experiments which show that exponentially growing animal cells whose ability to synthesize total protein has been inhibited with cycloheximide (by up to 70%) grow at rates approximately proportional to their rates of protein synthesis. However, virtually the entire elongation of the cell cycle occurs in the part of the GC phase that depends on a high concentration of serum in the medium. This part of the cycle has earlier been suggested to lie prior to the restriction point-i.e., the point beyond the main regulatory processes of G1. The remainder of the cycle, from restriction point to mitosis, is markedly insensitive to these concentrations of cycloheximide as well as to growth regulation. We quantitatively account for the specific lengthening of that part of the cycle involved in growth regulation by assuming that cells must accumulate a specific protein in a critical amount before they can proceed beyond the restriction point. The lability of this protein (half-life about 2 hr) makes its accumulation unusually sensitive to inhibition of total protein synthesis by cycloheximide. Its production appears to depend on growth factors provided by serum. The model can also account for greater variations of G1 durations as the growth of cell populations is made slower. It also predicts two sorts of quiescence: one of cells slowly traversing GC, in slightly suboptimal conditions; the other of cells that enter Go under inadequate conditions. Transformation of different sorts could create cells with altered variables for initiation, synthesis, or inactivation of the regulatory protein or could altogether eliminate the need for the protein.The proliferation rate of animal cells is largely determined by the relative times that they spend in the cell cycle as opposed to quiescence. In each cycle an initiation event is required to start another round of the cell cycle; in its absence cells enter a quiescent state in which they remain until initiation occurs (1). Growth appears to be determined by the cyclic occurrence of this initiation event; completion of the cycle is relatively unaffected by conditions of growth (2). Similarly, for bacterial growth (3) and for synthesis of nucleic acids and proteins, control is by frequency of initiation; subsequent events proceed at constant rates.We have defined completion of the growth-controlling event in the cell cycle as the restriction point R (1). When a growing culture (of 3T3 mouse cells) is shifted to a condition (medium containing 0.5% serum) that does not support continued growth (4, 5), R can be calculated from the fraction of cells that cannot leave the G1 phase to lie about 2 hr before the beginning of DNA synthesis (6). Work with chicken cells earlier indicated that R lies somewhere in mid-GC (7).The role of R point control is accentuated by studies of cells transformed to tumorigenicity by DNA tumor viruses (8-10). Wh...

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Section: Discussionsupporting

confidence: 64%

Synthesis of labile, serum-dependent protein in early G ₁ controls animal cell growth

Rossow

Riddle

Pardee

1979

Proc. Natl. Acad. Sci. U.S.A.

244

117

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“…at all (7). On the other hand, the presence of cycloheximide at 30-90 ng/ml during the same period retarded initiation of S phase by about 2-5 h (data not shown), confirming the previous results that the progression of cells is sensitive to cycloheximide almost throughout the prereplicative phase (10). These kinetic results clearly show that the inhibitory effects of the two drugs on the progression of prereplicative phase in serum-stimulated cells are different.…”

supporting

confidence: 86%

Blockage of prereplicative progression by cytochalasin D in serum-stimulated GC-7 cells.

Takasuka

Ishibashi

Ide

1987

Cell Struct. Funct.

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“…We demonstrated NDEA cytostatic effect (0.5 and 5mM) through a significant reduction in the mitotic index (MI) in a dose dependent manner (Table I). The delay observed in mitosis (Table I) could be due to the inhibition of DNA synthesis (Schneiderman et al 1971, Sudhakar et al 2001, Türkǒglu 2007 or to a blocking in the G2-phase of the cell cycle, preventing mitosis ( Van't Hof 1968, Türkǒglu 2007.…”

Section: Discussionmentioning

confidence: 99%

Ability of Allium cepa L. root tips and Tradescantia pallida var. purpurea in N-nitrosodiethylamine genotoxicity and mutagenicity evaluation

Rainho

Kaezer

Aiub

et al. 2010

An. Acad. Bras. Ciênc.

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N -nitroso compounds, such as N -nitrosodiethylamine (NDEA), can be formed by the reaction of secundary amines with nitrosating agents, and are suspected to be involved in tumors in humans. NDEA has been considered a weak carcinogen in genotoxic assays probably due to the inefficient nitrosamine activation system that is used and/or to the efficient repair system. In this work, we evaluated the sensibility of Allium cepa L. root tips and Tradescantia stamen hair mutation assay (Trad-SH) using Tradescantia pallida var. purpurea for NDEA (0.1; 0.5; 5 and 25mM) genotoxicity and mutagenicity induction. Allium cepa L. was treated with different NDEA concentrations for 3h, for 3 consecutive days, including negative control (distilled water) and positive control maleic hydrazide (MH 30μg/mL). After treatment, the roots were hydrolyzed, squashed, and the mitotic index (MI) and cytological abnormalities were scored. The results revealed a cytostatic effect of NDEA (0.5 and 5mM), showing a significant reduction in the MI. Chromosome stickiness suggests a NDEA toxic effect. T. pallida purpurea did not respond to mutagens with a dosedependent pattern. In conclusion, our study indicates that the root tips of Allium cepa L. have sensibility to detect NDEA genotoxicity, but not for Trad-SH test.

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Inhibition of DNA synthesis in synchronized Chinese hamster cells treated in G1 with cycloheximide

Cited by 186 publications

References 29 publications

Synthesis of labile, serum-dependent protein in early G ₁ controls animal cell growth

Synthesis of labile, serum-dependent protein in early G ₁ controls animal cell growth

Blockage of prereplicative progression by cytochalasin D in serum-stimulated GC-7 cells.

Ability of Allium cepa L. root tips and Tradescantia pallida var. purpurea in N-nitrosodiethylamine genotoxicity and mutagenicity evaluation

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Inhibition of DNA synthesis in synchronized Chinese hamster cells treated in G1 with cycloheximide

Cited by 186 publications

References 29 publications

Synthesis of labile, serum-dependent protein in early G 1 controls animal cell growth

Synthesis of labile, serum-dependent protein in early G 1 controls animal cell growth

Blockage of prereplicative progression by cytochalasin D in serum-stimulated GC-7 cells.

Ability of Allium cepa L. root tips and Tradescantia pallida var. purpurea in N-nitrosodiethylamine genotoxicity and mutagenicity evaluation

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Synthesis of labile, serum-dependent protein in early G ₁ controls animal cell growth

Synthesis of labile, serum-dependent protein in early G ₁ controls animal cell growth