Search PubMedSearch

PubMed · 1064742

Cell kill kinetics with hydroxyurea.

Abstract

The effects of various concentrations of hydroxyurea (HU) on a human lymphoid cell line in exponential growth phase have been studied using a combination of methods, including determination of the total and viable cell counts; the cells relative DNA content, measured in a flow microfluorimeter after staining with a fluorescent Feulgen technique; the mitotic index; and the percentage of cells incorporating thymidine-3H (TdR-3H) during brief and continuous exposure to the isotope both in the presence and absence of colcemid. A significant redistribution of the cells in the various phases of the cell cycle occurred during the first 24 hr of continuous treatment with 10(-3) M and 10(-2) M HU as follows: (1) division of cells in G2; (2) depletion of mid and late S phase cells due to early cell death; (3) movement of most G1 cells at a normal rate into early S phase where they accumulate; and (4) arrest of the remaining cells in G1, which represented the surviving population after treatment for 96 hr or longer. After removal of the drug, the cell fraction blocked in early S phase progressed semisynchronously through S, but many of the cells were unable to complete division. Their capacity to recover depended on the drug concentration and duration of exposure, but in general the cellular injury caused by HU was more reversible than that caused by "equivalent" concentrations of arabinosylcytosine.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

X Yataganas, A Strife, A Perez, B Clarkson. 1976. Cell kill kinetics with hydroxyurea.. https://doi.org/10.1002/mpo.2950020105

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Radiation doses to the cell nucleus in single cells and cells in micrometastases in targeted therapy with (131)I labeled ligands or antibodies.

PURPOSE: The aim of this study was to theoretically investigate how the radiation dose to cell nuclei depends on the subcellular position of (131)I. The influence of the size of the cells and crossfire irradiation in clusters of cells was also studied. METHODS AND MATERIAL: Using data describing the dose rate around a point source of (131)I, we calculated the dose distributions inside and around cell models of different sizes. The assumed positions of (131)I were on the cellular or nuclear membrane, in the cytoplasm, in the nucleus, or spread in the whole cell. The mean doses to the nucleus of the targeted cell and to the nuclei of its neighbors were calculated using the dose distributions. RESULTS: The dose distributions inside a single targeted cell showed very different distribution profiles depending on the subcellular position of the (131)I. Targeting the nucleus instead of the cellular membrane could increase the dose to the nucleus 10-fold. Crossfire irradiation can be the major contributor to the nuclear dose in clusters of more than six cells. CONCLUSIONS: Dosimetry without microscopic considerations is inadequate for targeted radionuclide therapy of disseminated or clustering tumor cells exposed to (131)I. Therapeutic doses could be achieved, even in single cells, when (131)I was positioned near, or inside the cell nucleus, or when the clusters were large enough.

Cell Count

The levels and kinetics of oxygen tension detectable at the surface of human dermal fibroblast cultures.

Low oxygen tension has recently been shown to stimulate cell growth and clonal expansion, as well as synthesis and transcription of certain growth factors and extracellular matrix components. These results have been obtained by exposing cell cultures to a hypoxic environment. Using an oxygen probe, we have now studied how experimental conditions affect the oxygen tension detectable at the cell surface. Dissolved oxygen tension was directly related to the height of the medium above the cell surface (r = 0.8793, P = 0.021), but was constant when no cells were present in the flask (r = -0. 9732, P = 0.001). In both human dermal fibroblasts and NIH/3T3 cultures, oxygen tension decreased linearly as cell density increased (r = -0.835, P < 0.0001; r = -0.916, P < 0.0001, respectively). When human dermal fibroblasts were exposed to 2% O(2), maximum hypoxic levels (0 mmHg) were achieved within approximately 15 min, and the recovery time was within a similar time frame. The addition of rotenone, an inhibitor of cellular respiration, blocked this decrease in oxygen tension at the cell surface, suggesting that cellular consumption of oxygen is responsible for the decline. Finally, we examined the cell-surface oxygen tension in control and acutely wounded human skin equivalents (HSE), consisting of a keratinocyte layer over a type I collagen matrix containing fibroblasts. We found that oxygen tension dropped significantly (P < 0.0001) in acutely wounded areas of HSE as compared to unwounded areas of HSE and that this drop was prevented by the addition of mitomycin C. These results indicate that cell-surface oxygen tension is indirectly related to cell density, and that the amount of detectable oxygen at the cell surface is a function of cell density, the oxygen tension in the incubator, and increased cellular activity, as occurs after injury.

Cell Count

[Inhibition of proliferation of retinal pigment epithelium in vitro: vitamin A pharmacodynamics I].

BACKGROUND: In proliferative vitreoretinopathy and choroidal neovascularization, retinal pigment epithelial (RPE) cells proliferate among other cell types. Cell proliferation is controlled by many factors. One such factor is the "superfamily" of nuclear receptors. Ligands of these receptors are vitamin A and D, triiodothyronine and dexamethasone. All-trans-retinal (atR) inhibits human RPE-cell proliferation. AtR binds to the nuclear ligand-dependent transcription factors RAR (retinoic acid receptor) and RXR (retinoid X receptor). Pharmacodynamics of atR were investigated with respect to inhibition of RPE cell proliferation. MATERIALS AND METHODS: Primary human RPE cell lines were used up to passage 5. RPE cells were incubated with atR ranging from 1 pM up to 1 microM. AtR was added every other day for 7 days. Cell proliferation was determined by cell counting. RESULTS: AtR inhibited RPE cell proliferation in a biphasic manner. Two IC50 values were calculated, one in the picomolar range, 10 pM (5-24, 95% confidence interval) and one in the nanomolar range, 17 nM (8-37). Furthermore, inhibition of cell proliferation was examined using specific RAR agonists. Agonists of the RAR-b subgroup inhibited cell proliferation at the lowest concentrations. CONCLUSIONS: RPE cell proliferation in vitro is inhibited by agonists of RAR. Agonists of the RAR-b subgroup inhibit RPE cell proliferation at the lowest concentrations.

Cell Count