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Biomedical subjects

B Palcic

Publications and source records attributed to B Palcic.

At least 91 records · Page 5Linked to original sources
PubMed1986

Cell motility measurements with an automated microscope system.

The motility of 3T3 cells has been studied using a newly developed automated microscope system which is capable of recognizing live unstained cells growing in tissue culture. A large number of individual cells can be rapidly identified and characterized and their precise positions recorded. All cells can be revisited automatically every few minutes, and the new cell positions can be determined. Quantitative data from up to 1 000 cells can then be obtained, and cell movement parameters like cell speed, distance travelled, direction of movement, etc., can be measured for individual cells and for the whole cell population. In addition, for any number of chosen cells, high-resolution digitized images can be taken for further morphological studies, including acquisition of images of individual cells.

Animals↗
PubMed1986

Radiosensitization of hypoxic cells at low doses.

We have measured the radiosensitization produced in hypoxic V79 cells in vitro by SR 2508, Ro-03-8799, and oxygen at conventional doses (0-30 Gy) as well as at low doses (0-4 Gy). Two techniques have been used: (a) FACS (Fluorescence Activated Cell Sorter) plating followed by the conventional colony formation assay and (b) microscopic scoring of surviving and non-surviving cells using the DMIPS (Dynamic Microscope Image Processing Scanner) system. The results show that the enhancement ratios (ER) for both drugs and for oxygen are dose dependent, decreasing somewhat at doses less than 4 Gy. The low dose sensitization measured at S = 0.8 for SR 2508, Ro-03-8799 and O2 was found to be approximately 73%, 61% and 75% of the high dose sensitization for these three agents, respectively. These values are not significantly different. Both the alpha- and beta-components of cell kill appeared to be sensitized by all three agents. The enhancement ratios obtained by the two different techniques are in general agreement, though some qualitative differences have been observed.

Animals↗
PubMed1986

The use of solid-state image sensor technology to detect and characterize live mammalian cells growing in tissue culture.

Arguments are presented that approximately 30 000 cells have to be measured in a single experiment to measure radiobiological parameters in a low-dose survival assay. For this purpose, a fully automated device capable of detecting and recognizing individual live unstained mammalian cells at a rate of 1 cm2/min is required. Specifications of such a system are derived and evidence is presented which suggests that this can best be carried out using a solid-state image sensor in the form of a linear array of photodetectors. The outline of the design and other potential uses of such a device are discussed.

Animals↗
PubMed1985

Bleomycin and misonidazole cytotoxicity.

Chinese hamster ovary (CHO) cells were exposed in vitro to combinations of bleomycin and misonidazole under hypoxic conditions. Only one drug was present at any given time and cells were washed before being exposed to the second drug. Both drugs induced potentially lethal damage (PLD). This damage was repaired under hypoxic conditions very rapidly, and bleomycin-induced PLD was repaired more rapidly than misonidazole-induced PLD. If, after the combined treatment, cells are kept in hypoxia, much of the damage can be repaired.

Animals↗
PubMed1985

In vitro and in vivo studies of the TRIUMF pion therapy beam.

Patient treatments at TRIUMF (Tri-University Meson Facility, Vancouver, B. C.) use a moving spot raster scan technique where the pion range is modulated in depth for each position of the moving spot. The spot scans in a stepwise fashion and can produce any desired field shape. This approach provides very good dose uniformity across the treatment field and allows maximum flexibility in shaping the treatment volume. Survival of cultured cells has been used as a biological dosimeter to test the isoeffectiveness of the pion dose distributions, which must be shaped in depth to compensate for the depth-dependent LET distribution. Isoeffectiveness across the treatment field has also been verified using this system, which involves irradiating cells supported in a gelatin matrix. The response of pig skin to pion irradiation at TRIUMF has provided a check on the in vivo RBE for acute effects derived from our earlier studies with mouse foot. In addition, the pig skin reactions have been followed for several months to assess the later dermal response. The RBE of our pion beam relative to 270 kVp X rays is approximately 1.5 for both the acute epidermal and the later dermal responses.

Animals↗
PubMed1984

In vivo and in vitro mechanisms of radiation sensitization, drug synthesis and screening: can we learn it all from the high dose data?

The evidence for a decreased enhancement ratio of oxygen and an electron affinic radiosensitizer (misonidazole) at low doses is presented, and the mechanism of this effect is discussed. The factors which influence the magnitude of this effect, as well as the dose levels at which the effect will be significant, are identified. This will allow further characterization of this phenomenon in the future. An approach by which present and new hypoxic radiosensitizers could be made more effective at low doses is indicated.

Animals↗
PubMed1984

Reduced oxygen enhancement ratio at low doses of ionizing radiation.

A decreased oxygen enhancement ratio (OER) at lower radiation doses has been previously reported (B. Palcic, J. W. Brosing, and L. D. Skarsgard, Br. J. Cancer 46, 980-984 (1984]. The question remained whether or not this effect is due to a possible oxygen contamination at low doses, which was not the case at high doses. To ensure a sufficient degree of hypoxia prior to the start of irradiation, Chinese hamster cells (CHO) were made hypoxic by gas exchange combined with metabolic consumption of oxygen at 37 degrees C. At the same time oxygen levels in cell suspension were measured using a Clark electrode. It was found that under experimental conditions used in this laboratory for hypoxic irradiations, the oxygen levels before the start of irradiation are always below the levels which could give any significant enhancement to radiation inactivation by X rays. Full survival curves were determined in the dose range 0-30 Gy using the conventional survival assay and in the dose range 0-3 Gy using the low dose survival assay. The results confirmed the earlier finding that the OER decreases at low doses. It is therefore believed that the dose-dependent OER is a true radiobiological phenomenon and not an artifact of the experimental method used in the low dose survival assay.

Animals↗
PubMed1984

The effect of misonidazole as a hypoxic radiosensitizer at low dose.

Using an automated low dose survival assay, the radiosensitizing effectiveness of misonidazole at low radiation dose (0-6 Gy) was measured in cultured mammalian cells. Also measured was its effectiveness at high doses of radiation (0-35 Gy) using the conventional survival assay. In both cases, several concentrations of the drug from 0 to 5 mM were used. The data at low doses were analyzed by a two-parameter mathematical equation with linear and quadratic dose terms, S = e-alpha D-beta D2, which proved to be a good fit to the experimental data at all misonidazole concentrations. It is shown that whereas the coefficient of the quadratic dose term, beta, increases significantly with increasing misonidazole concentration, the drug does not significantly affect the coefficient of the linear term, alpha. The enhancement ratio (ER) of misonidazole is shown to be decreased at lower doses. The clinical implications of this result are discussed.

Animals↗
PubMed1982

Ocular absorption and toxicity of a radiosensitizer and its effect on hypoxic cells.

The recurrence of retinoblastoma after radiation treatment may be related to hypoxic cell radioresistance. Radiosensitizing drugs acting on hypoxic cells without affecting the response of oxygenated cells could improve treatment of ocular tumors while minimizing complications of radiotherapy. A desmethyl derivative of misonidazole is as effective a radiosensitizer as misonidazole (as measured in vitro) and is better suited to ocular administration, since it is more soluble than misonidazole. We studied the ocular toxic effects of a desmethyl derivative of misonidazole after subconjunctival administration of 140 and 70 mg. The higher dose produced an intolerable ocular toxic effect, but at the lower dose, the toxic effect was moderate and reversible. We compared ocular pharmacokinetics of the desmethyl derivative of misonidazole after subconjunctival and intravenous (IV) injections. Subconjunctival administration yielded vitreous and anterior chamber concentrations of the radiosensitizer sufficient to produce a notable dose-modifying effect (as high as 1.8 in the anterior chamber and 1.25 in the vitreous at 70-mg doses). In contrast, even at doses of 140 mg, IV injections of the desmethyl derivative of misonidazole did not result in therapeutically useful ocular levels.

Animals↗
PubMed1982

Radiobiology of pions at TRIUMF.

Radiobiological studies at TRIUMF of the effects of pion beams have been carried out using cultured cells, mice and pigs. CHO cells in gel/medium were used for RBE determinations throughout the dose distributions. The RBE was shown to increase with depth in the stopping region, while the average RBE value decreased with increasing width of the stopping peak and also increased with increasing field size. The results suggest that the effects of peak width and field size will approximately cancel out when treatment volumes are changed, provided that all three dimensions are changed more or less proportionally. The peak center RBE values ranged from 1.2-1.3 for single doses. The oxygen enhancement ratio (OER) for pions was 2.2 compared to 2.8 for X rays. Split dose recovery was found to be somewhat reduced in the peak region. In vivo studies with mouse and pig skin have been done for 1 to 20 fractions. For mouse skin, pions showed an RBE of 1.5-1.6 for fraction numbers greater than 10. The RBE for pig skin was 1.4 for early reactions, but it may be higher for medium term reactions.

Animals↗
PubMed1981

In vitro metabolism of misonidazole.

Misonidazole (MISO) is a nitroimidazole drug currently undergoing clinical trials as a radiosensitizer of hypoxic tumour cells. The drug is also toxic to such cells, probably because of metabolic activation of the nitro group under hypoxia. The metabolic fate of 14C-labelled MISO is examined, using hypoxic mammalian (CHO) cells in vitro. Organic-soluble and acid-soluble metabolites are formed, and radioactivity is bound to macromolecules. The organic-soluble products are separated by TLC and HPLC. Evidence is presented to show that one of the metabolites is hydroxylamino-misonidazole. The significance of metabolic nitroreduction is discussed.

Animals↗
PubMed1981

Modification of the action of misonidazole. III. The effect of diamide on toxicity and radiosensitization.

Diamide, a compound which depletes cells of reduced glutathione, decreases toxicity of misonidazole to hypoxic cells, as measured by single-strand break (SSB) production, cell inactivation, and uptake of radioactive misonidazole. As a radiosensitizer, the effect of diamide in cell pellets is additive to that of misonidazole. Individually, both misonidazole and diamide enhance SSB production in DNA of cells irradiated under hypoxia in dilute suspension, but a combination of the two drugs does not appear to produce a greater number of SSB than misonidazole alone.

Animals↗
PubMed1980

Lesions in DNA of hypoxic mammalian cells irradiated in the presence of TAN.

TAN (triacetoneamine-N-oxyl) at a concentration of 10 mM gives a dose modifying factor (DMF) of 1.45 for the surviving fraction of gamma-irradiated hypoxic mammalian cells. Under the same conditions, however, TAN produces little or no enhancement of single strand breaks (SSB) in DNA (DMF congruent to 1). In this study, enhancement of the type of DNA lesions exposed by an extract of M. luteus is reported. The DMF for this type of damage (MLS) is 1.5. TAN is known to affect the size of DNA synthesized after irradiation, presumably by causing interruptions in synthesis at TAN-DNA adduct sites. The absolute number of M. luteus extract sensitive sites detected in this work corresponds to approximately on half of the number of sites of interrupted synthesis. In its sensitizing effect on DNA, the free radical TAN is different from the electron affinic drug, misonidazole.

Animals↗
PubMed1980

Modification of the action of misonidazole. I. Effect of TAN on toxicity.

The toxicity of misonidazole, an electron affinic radiosensitizer, is greatly reduced by TAN, a free radical radiosensitizer. The production of single-strand breaks in DNA of mammalian cells incubated in dilute suspension with misonidazole (15 mM) under hypoxic conditions is greatly decreased by the presence of TAN (10 mM). The survival of such cells is also greatly enhanced if TAN is present at a concentration of 10mM even less. The implications and possible mechanisms of this finding are discussed.

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