X-Ray and Ultraviolet Sensitivity of Synchronized Chinese Hamster Cells at Various Stages of the Cell Cycle

Sinclair, Warren K.; Morton, R. A.

doi:10.1016/s0006-3495(65)86700-5

Cited by 282 publications

(51 citation statements)

References 21 publications

(40 reference statements)

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“…(Similar studies relative to the variation of radiation-induced cell killing through the cycle of Chinese hamster cells have been reported [10] .) We present here our results with this antibiotic and we will report elsewhere a detailed comparison between cycle-dependent killing due to actinomycin D, radiation, and the bifunctional alkylating drug nitrogen mustard when these agents are used singly and together .…”

Section: Introductionsupporting

confidence: 60%

Cell Killing by Actinomycin D in Relation to the Growth Cycle of Chinese Hamster Cells

Elkind

Kano

Sutton-Gilbert

1969

The Journal of Cell Biology

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Using Chinese hamster cells in culture, we have measured the effectiveness of actinomycin D to suppress division as a function of the position, or age, of a cell in its growth cycle . Cells were first exposed to millimolar concentrations of hydroxyurea in order to produce a synchronized population just before the onset of DNA synthesis . Thereafter, the survival response after 30 min exposures to actinomycin D was measured . Cells become resistant as they enter the S phase and then sensitive again in the latter part of S . When they reach G2 (or G 2-mitosis) they are maximally resistant ; at 1 .0 µg/ml, for example, the survival in G 2 is 30-fold greater than it is in G 1 . These results, plus measurements reported earlier on the interaction of damage in S cells due to actinomycin D and X-irradiation, suggest that the age-response pattern of the toxic effects of this drug probably reflects both the functional capacity of DNA-actinomycin complexes and the ability of this antibiotic to penetrate chromatin and bind to DNA .

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Section: Introductionsupporting

confidence: 60%

Cell Killing by Actinomycin D in Relation to the Growth Cycle of Chinese Hamster Cells

Elkind

Kano

Sutton-Gilbert

1969

The Journal of Cell Biology

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“…Nab-paclitaxel induced mitotic arrest that lasted for 4 days after administration, although it peaked at 9 h. Earlier studies showed that solvent-based taxane -induced G 2 -M arrest is a major mechanism underlying radioenhancement produced by these agents (33) because G 2 -M cells are known to be more radiosensitive than cells in other phases of the cell cycle (34). Although this mechanism was likely involved in the presently observed enhancement of tumor radioresponse, it probably was not the dominant mechanism because radiation delivered at the peak of mitotic arrest was not the most effective combination schedule (enhancement factor = 1.3).…”

Section: Discussionmentioning

confidence: 99%

130-nm Albumin–Bound Paclitaxel Enhances Tumor Radiocurability and Therapeutic Gain

Wiedenmann

Valdecanas²,

Hunter³

et al. 2007

Clinical Cancer Research

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Purpose: 130-nm albumin^bound paclitaxel (nab-paclitaxel) is a novel solvent-free albuminbound paclitaxel, designed to avoid solvent-related toxicity. Nab-paclitaxel has been successfully introduced into the clinic but its radiation-enhancing potential has not yet been evaluated. We conducted a preclinical evaluation of the radiation-modulating effects of nab-paclitaxel in tumor and normal tissues. Experimental Design: Mice bearing syngeneic ovarian or mammary carcinomas were treated with nab-paclitaxel, radiation, or combination of both. Nab-paclitaxel was administered at 90 mg/kg, 1.5 times the maximum tolerated dose for solvent-based paclitaxel. End points were antitumor efficacy (growth delay, radiocurability, and cellular effects) and normal tissue toxicity (gut and skin). Results: Nab-paclitaxel showed single-agent antitumor efficacy against both tumor types and acted as a radiosensitizer. Combined with radiation, nab-paclitaxel produced supra-additive effects when given before radiation. Nab-paclitaxel significantly increased radiocurability by reducing the dose yielding 50% tumor cure (TCD 50 ) from 54.3 to 35.2 Gy. Tumor histology following nab-paclitaxel treatment was characterized by pronounced necrotic and apoptotic cell death and mitotic arrest. Nab-paclitaxel did not increase normal tissue radioresponse. Conclusions: Nab-paclitaxel exhibited strong antitumor efficacy against both tumors as a single agent and it improved radiotherapy in a supra-additive manner. These improved effects were achieved without increased normal tissue toxicity to either rapidly or slowly proliferating normal tissues although the drug dose was 1.5 times higher than the maximum tolerated dose of solventbased paclitaxel. These preclinical findings show that combining nab-paclitaxel with radiotherapy would improve the outcome of taxane-based chemoradiotherapy. This novel taxane is thus a good candidate for testing in clinical chemoradiotherapy trials.Besides being very efficient cytotoxic drugs on their own, taxanes are also potent enhancers of tumor radiation response. In the clinical setting, taxanes are being used as radiationenhancing drugs in a variety of disease sites including nonsmall-cell lung cancer, head and neck, esophageal, gastric, cervical, urothelial, and nasopharyngeal carcinoma (1 -7).Taxanes are complex diterpenoids characterized by an extremely hydrophobic structure with sparse aqueous solubility (8). To overcome solubility problems, chemical solvents such as ethanol, Tween 80, and castor oil (Cremophor EL) are used in currently approved solvent-based taxane formulations. These solvents are known to cause biological and pharmacologic side effects, including dose-limiting toxicity, acute hypersensitivity reactions, and altered pharmacokinetics (resulting in a nonlinear pharmacokinetic profile). As a result, intensive research is being aimed at developing alternative formulations (8 -12).One such alternative is nab-paclitaxel (Abraxane), a novel, solvent-free 130-nm nanoparticle albumin -bound formu...

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“…The effects noted though were sometimes small, and work with asynchronous ce 11 s has the added compl i cat i on that effects observed represent that of a heterogeneous population. It is well known that the radiation sensitivity of mammalian cells varies dramatically through the cell cycle (Terasima and Tolmach, 1961;Sinclair and Morton, 1965). …”

Section: Synchronized Cellsmentioning

confidence: 99%

Role of protein synthesis in the repair of sublethal x-ray damage in a mutant Chinese hamster ovary cell line

Yezzi¹

1985

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X-Ray and Ultraviolet Sensitivity of Synchronized Chinese Hamster Cells at Various Stages of the Cell Cycle

Cited by 282 publications

References 21 publications

Cell Killing by Actinomycin D in Relation to the Growth Cycle of Chinese Hamster Cells

Cell Killing by Actinomycin D in Relation to the Growth Cycle of Chinese Hamster Cells

130-nm Albumin–Bound Paclitaxel Enhances Tumor Radiocurability and Therapeutic Gain

Role of protein synthesis in the repair of sublethal x-ray damage in a mutant Chinese hamster ovary cell line

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