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Biomedical subjects

J G Szekely

Publications and source records attributed to J G Szekely.

At least 19 recordsLinked to original sources
PubMed1992

The effect of gamma-irradiation on the toxicity of malathion in V79 Chinese hamster cells and Molt-4 human lymphocytes.

There is growing interest in the irradiation of food and agricultural products for insect disinfestation, sprout inhibition, delayed ripening and the reduction of microbiological loads. Extensive research has been done on this process, and irradiation to a maximum dose of 10 kGy is recognized as safe by national and international regulatory agencies. The question has been raised, however, whether irradiation of pesticide residues might produce radiation products that were more toxic or less toxic than the original pesticide. To address this question, we observed the effects of 10 kGy of gamma-radiation on malathion as measured by sister-chromatid exchange (SCE), micronuclei formation, cell survival, growth rate and polyploid formation. We found no significant differences between the effects of irradiated and unirradiated malathion on any of these end-points. Polyploid formation was the most dramatic effect of both irradiated and control malathion on V79 Chinese hamster cells. Cell survival, polyploid formation and growth rate were slightly better in cells treated with irradiated malathion. In Molt-4 human lymphocyte cells, micronuclei formation was not affected by irradiated or unirradiated malathion. Compared to malathion alone, the lack of such biological effects indicates that none of the presumed radiation-induced breakdown products increased or decreased the endpoints studied. The number of SCE was consistently, but not significantly, higher in the cells treated with irradiated malathion. There were no significant differences in cell survival or micronucleus formation in the human lymphocyte cell line Molt-4 treated with irradiated or control malathion. Thus, the irradiation of the pesticide malathion to 10 kGy, a recommended upper dose for most food irradiations, does not significantly alter its toxicity in these in vitro systems.

Animals↗
PubMed1992

The effect of colcemid on the heat survival of mitotic V79 Chinese hamster cells.

V79 Chinese hamster cells were collected by colcemid addition to study the effect of heat on mitosis. When they were heated at 42 degrees C and 45 degrees C in the presence of 0.06 micrograms/mL colcemid, cell survival increased over the control samples, which were heated in ordinary medium. Scanning electron microscopy showed that cells heated to 45 degrees C in the presence or absence of colcemid had fewer microvilli on the surface, but they did not have increased bleb formation. Transmission electron microscopy showed that the chromatin was diffuse in the heated cells and the kinetochores were indistinct. The mitochondria in the heated cells were also swollen and contained visible particles.

Animals↗
PubMed1991

Variants of Aspergillus alutaceus var. alutaceus (formerly Aspergillus ochraceus) with altered ochratoxin A production.

The present studies, using Aspergillus alutaceus var. alutaceus Berkeley et Curtis (formerly A. ochraceus Wilhelm) NRRL 3174 along with three other wild-type strains, were undertaken in an attempt to understand the effects of irradiation and other treatments on mycotoxin production in grain. Bedford barley was inoculated with spores of NRRL 3174, gamma irradiated, and incubated at 28 degrees C and 25% moisture. After 10 days of incubation, two colony types, ochre (parental) and yellow (variant), were isolated from the grain. Further culturing of the yellow variant resulted in the spontaneous appearance of a white variant that exhibited greatly enhanced fluorescence under UV light. In subsequent work, we have also isolated variants producing a soluble red pigment. In addition, in model experiments involving irradiation (1 kGy) of pure cultures, induction frequencies ranging between 2 and 4% (survival basis) were observed for the yellow and red variants. Inoculation of these variants into wheat and incubation for 14 days at 28 degrees C and 32% moisture resulted in ochratoxin A production in the relative amounts of 0.09:1:4.6:9.3 for the red, ochre (parental), yellow, and white variants, respectively. Additional characteristics of these isolates are described. Confirmation that the white high-ochratoxin-A-producing variants were derived from the parental strain was demonstrated by obtaining revertant sectors in monoclonal cultures of the variants.

Aspergillus ochraceus↗
PubMed1989

Morphological effects of lonidamine on two human-tumor cell culture lines.

Lonidamine, 1-(2-4-dichlorobenzyl)-1-H-indazol-3-carboxylic acid, is an anticancer drug that has its primary action on cellular metabolism rather than cell division. Since lonidamine is not effective in all tumor cells, we have tested it in two human-tumor cell culture lines: MOLT-4, a T-leukemia and U-87 MG, a glioma. Lonidamine exposure of MOLT-4 cells at 50 micrograms/mL and pH 6.7 disrupted the mitochondria within 1 h of treatment. The mitochondria were swollen and the cristae were disrupted. When the treated cells were re-incubated in fresh medium at pH 7.4 the mitochondria rapidly returned to their normal morphology. The U-87 MG glioma cells did not show ultrastructural disruption after 1-h treatment with lonidamine at concentrations up to 200 micrograms/mL at pH 6.7. In the concentration range of 25 micrograms/mL to 200 micrograms/mL, lonidamine did not produce any cell killing in MOLT-4 after a 1-h exposure at pH 7.4, although the drug had some limited effectiveness at pH 6.7. Compared to sham-treated controls, long exposures to 100 micrograms/mL of lonidamine at pH 6.7 reduced survival in MOLT-4 to 92% and 53% after 6-h and 24-h exposures, respectively. Survival of U-87 MG glioma cells was also strongly pH dependent, a 2-h exposure to 50 micrograms/mL lonidamine at pH 7.4 did not cause cell death; however, survival dropped to 84% of the control at pH 6.65.

Antineoplastic Agents↗
PubMed1988

The use of immunostaining to quantify x-ray and heat-induced multiple microtubule organizing centers in normal and transformed cells.

Microtubule organizing centers (MTOC) in control, irradiated and heated C3H 10T1/2 mouse embryo cells and two radiation-transformed sublines, R1 and R25, were made visible by indirect immunofluorescence using antibody against tubulin. The MTOC were reformed by 5-min incubation in fresh medium after the microtubules were depolymerized with nocodazole. The R1 line had a different distribution of MTOC/cell than the parent 10T1/2 line or R25, which had similar distributions. After irradiation, multiple MTOC appeared in the normal and radiation-transformed cells irradiated to 10 Gy and incubated for 24 or 48 h. The multiple foci of microtubule reformation in the irradiated cells indicate that radiation damage is expressed in structural elements in the cytoplasm. After heat treatment of the three cell lines (43 degrees C for 93 min and 45 degrees C for 25 min), the MTOC were disrupted and many cells did not have visible organizing centers at 24 or 48 h, while others had a large number of small centers of microtubule reformation. The distribution of MTOC/cell seen in R25 cells after the treatment had similar patterns to those of the 10T1/2 line rather than to those of the other radiation-transformed line, R1. Thus, the radiation or heat response seen in the MTOC is not dependent upon cell transformation.

Animals↗
PubMed1988

Thermal enhancement of cellular radiation damage: a review of complementary and synergistic effects.

Hyperthermia treatment can kill mammalian cells in a time and temperature dependent manner. Thermal sensitivity varies extensively among various cell lines in culture and cellular molecular and ultrastructural studies have not resolved which cellular mechanisms underlie thermal cell killing and radiosensitization. The response of cells to heat and radiation are complementary under certain conditions found in human tumors, such as hypoxia, low pH, low nutrient and the S-phase of the cell cycle. Thus, hyperthermia can be used as a complementary treatment modality in the radiotherapy of human cancer. Further studies show that heat treatment causes radiosensitization which is in part associated with the inhibition of repair of radiation damage and is strongly dependent on temperature and on the sequencing. In addition, the conditions such as pH and oxygenation during treatment sequencing can influence the degree of recovery of cells. These factors may be exploited in optimizing therapeutic gain in clinical cancer therapy. Data are shown that transformation from the normal to the tumorigenic state causes random small changes in radiosensitivity and heat sensitivity. Also, treatments combining heat and radiation can lead to increased or decreased transformation in cells depending on the treatment sequence.

Anaerobiosis↗
PubMed1987

The effect of glutathione depletion by diamide, diethyl maleate or buthione sulfoximine on the surface structure of mouse L-cells.

Radiosensitizers that act by reducing glutathione levels have been studied by many workers as agents to enhance the killing of hypoxic tumour cells. In this paper we describe a scanning electron microscope (SEM) study of the surface morphology of mouse L-cells after exposure to three of these: diazenedicarboxylic acid bis N,N-dimethylamide (diamide), DL-buthionine-S,R-sulfoximine (BSO) and diethyl maleate (DEM). Diamide at 0.1 to 0.6 mMol/L for 10 min produced large blebs on the cell surface as seen in the SEM. Transmission electron microscope (TEM) images show that these are clear, featureless regions of cytoplasm. BSO treatment for 24 h at 0.5 to 2.0 mMol/L, by contrast, left the surface similar to control cells. DEM at 0.5 mMol/L for 2 h produces small blebs over the cell surface and a reduction in the number of microvilli. A combined 24 h BSO treatment with 2 h of DEM produced large blebs, which were similar in TEM micrographs to those produced by diamide. Thus, although all three sensitizers reduce glutathione levels, they have different effects on cellular morphology and hence such secondary effects may account for the different degrees of radiation sensitization seen with these agents.

Animals↗
PubMed1987

The use of flow cytometry to measure glucocorticoid-induced killing of lymphoid cell lines.

A flow cytometer method was developed to measure glucocorticoid-induced death in sensitive lymphoid cells. The murine lymphoma cell lines, R1.1, S49.1 and WEHI 7.1, and the human T-lymphocyte cell line, MOLT-4, were exposed to 10(-8) to 10(-6) mol/L dexamethasone or methylprednisolone. The cytogram for unstained, unfixed cells, produced by plotting the axial light loss versus the right-angle scatter using a He-Ne laser as the light source, showed two clearly separated peaks corresponding to live and dead cells. The ratio of live to dead cells seen in the cytogram correlated with that obtained by trypan blue staining. The flow cytometry method offers a number of advantages: 300 to 500 cells/s can be counted, yielding speed and good counting statistics; unstained, unfixed cells can be used; and the live and dead cells can be sorted for plating or biochemical analysis. S49.1 and R1.1 cells were sensitive to methylprednisolone and dexamethasone in the 10(-6) to 10(-8) mol/L concentration range, while MOLT-4 and WEHI 7.1 cells were less sensitive. After a 48-h exposure to 10(-8) mol/L dexamethasone, S49.1 and R1.1 cell cultures had 30% and 38% dead cells, respectively, while WEHI 7.1 and MOLT-4 cell cultures had less than 5% dead.

Animals↗
PubMed1985

The use of flow cytometry to measure X-ray survival in cultured T lymphocytes.

Light-scattering signals produced in a flow cytometer containing unstained, irradiated T-lymphocytes (MOLT-4 cell line) were analysed by plotting the axial light loss versus right-angle scatter. The resulting three-dimensional scattergram separated into two regions, corresponding to live and dead cells, as confirmed by trypan blue staining. The method is simple, rapid, allows large numbers of cells to be measured, avoids staining artifacts and is suitable for measuring radiation-induced killing down to 0.5 to 0.1 Gy.

Cell Line↗
PubMed1985

High radiosensitivity of the MOLT-4 leukaemic cell line.

Radiation survival of MOLT-4, a leukaemic T-lymphocyte cell line, was measured by counting colonies formed in 0.8 per cent methyl cellulose. The survival curve was a simple exponential and showed the cells to be radiation sensitive, with D0 = 0.49 +/- 0.02 Gy and extrapolation number n = 0.92 +/- 0.09. No increase in survival as measured by colony-forming ability or trypan blue dye exclusion was seen when the dose was split into two fractions, separated by a 5 h incubation period. Electron microscopy and trypan blue dye exclusion showed that 5 h after exposure to high doses, MOLT-4 cells began to die and displayed condensed, marginated chromatin and cellular vesiculation.

Adult↗
PubMed1985

Growth of a radiation-transformed clone of C3H 1OT1/2 cells into melanin-producing colonies.

When R25, a radiation-transformed clone of C3H 1OT1/2 cells, was plated in soft agarose, a fraction of the colonies became pigmented. The morphologies of the white and dark colonies and their cells were compared by optical, transmission and scanning electron microscopy. The transformed R25 cells had apparently differentiated into melanin-producing cells in the soft agarose, with the white colonies containing actively growing cells having only a few melanosomes, and the dark colonies being made up of stationary-phase cells filled with electronopaque melanosomes. Exposure of the R25 cells to 4.0 Gy of X-rays decreased the percentage of dark colonies, while exposure to 1% DMSO had no effect.

Animals↗
PubMed1984

Simulated responses to intermittent lognormally distributed doses at variable dose rates.

Two previously reported equations for low-LET radiation, R = DmI-n and R = D[a + b(lnI) + h(lnI)2], where the response (R) is expressed in terms of dose (D) and dose rate (I) and the other parameters are constants, were used to compute distributions of response to intermittent, low-level, lognormally distributed doses, administered at different dose rates. The simulations show that the means of the response distributions are affected by both the dose and dose rate distributions. Within certain ranges of their respective values, the influence of the dose and dose rate on the response are in opposite directions, and lead to similar response distributions for numerically different combinations of dose and dose rate. The resolution and mean values of response distributions, when based on nonlinear dose-response relationships, are also affected by dose fractionation.

Animals↗
PubMed1983

Effect of anisotonic NaCl treatment on cellular ultrastructure of V79 Chinese hamster cells. Part 1. Mitotic cells.

The ultrastructural modifications produced by anisotonic NaCl treatment of Chinese hamster mitotic cells were observed at three NaCl concentrations which have been frequently used in radiosensitization studies: 0.05, 0.5 and 1.5 M. After exposure to 0.05 M NaCl, many well-spread chromosomes are visible. The chromatin fibres are well dispersed and membraneous material is associated with the chromosomes. After hypertonic treatment with 0.5 M NaCl, the chromosomes have a uniform, structureless appearance with some coalescing into larger anaphase-like masses. At 1.5 M NaCl, large scale cellular dehydration is apparent, and filamentous structures such as microfilaments are tightly constricted. The degree of chromosome staining is also reduced below the level of the cytoplasm. After both hypo- and hypertonic NaCl treatment the chromosomes appear swollen relative to untreated cells, but hypertonic treatment causes chromosome clumping and dissociates chromatin. Conformational changes in the chromatin may restrict the capacity for DNA repair and be related to cellular radiosensitivity.

Animals↗
PubMed1983

Simulated responses to lognormally distributed continuous low radiation doses.

Three previously reported equations, expressing response as a function of both dose and dose rate, for low LET radiation were used to compute distributions of response to continuous, low-level, lognormally distributed doses for populations of variable size up to 5000. The simulations show that, when the response is inversely dependent on dose rate, the mean of the response distribution can either increase or decrease with increasing exposure to radiation, depending on whether or not the dose-dependent term is the dominant one in an equation. In one equation, which defines the response as conjugated hydroperoxide formation in irradiated membranes, the magnitude of the dose-dependent term is reduced the most by superoxide dismutase, an enzymic inhibitor of free radical processes. This results in the means of response distributions decreasing with increasing dose from continuous, low-level radiation.

Animals↗
PubMed1983

Temperature dependence of anisotonic NaC1 effect on radiosensitization and ultrastructure of V79 Chinese hamster cells.

Isodose radiation survival of V79 Chinese hamster cells, pretreated with strongly hypertonic concentrations of NaC1 at 22 degrees C, or at 37 degrees C, has been determined and correlated with ultrastructural changes within the nucleus. After an exposure of less than 10 min to 1.5 M NaC1, at both temperatures, the cells are radioprotected, but after longer exposures, the cells treated at 37 degrees C are radiosensitive, whereas those treated at 22 degrees C still show protection. The cells are radiosensitized at both temperatures by pretreatment with 0.5 M and 0.05 M NaC1. The ultrastructure of the nucleus observed after the anisotonic treatments suggests that contraction or swelling of chromatin may be associated with the observed variation in radiation sensitivity.

Animals↗
PubMed1982

Effect of X-irradiation and radiation modifiers on cellular ultrastructure.

Ultrastructural changes produced in cultured cells after irradiation by X-rays reflect the temporal development of the original lesions. Alterations in membrane structures, especially the plasma and nuclear membranes, are documented, supporting the suggestion that membrane and membrane-DNA attachment sites are relevant to radiation-induced cell killing. Alterations produced by the radiosensitizer diamide and by anisotonic salt treatments were also observed. Diamide, at 0.4 to 0.6 mmol/L, rapidly decreased the active uptake of K+ ions at the plasma membrane and produced clear, organelle-free regions of cytoplasm and distorted nuclei. Anisotonic NaCl treatment of mitotic cells swells chromosomes under both hypo- and hypertonic conditions, leaving the chromatin open to free-radical attack. In interphase, the cell is drastically shrunken during the first few minutes of hypertonic (1.5 mol/L NaCl) salt treatment, after which breaks and localized blebs appear at the plasma membrane, while the nucleus swells, leaving the chromatin in an open state. This process occurs more quickly at 37 degrees C than at room temperature (22 degrees C) and correlates with the relative radiosensitivity of cells treated at these temperatures.

Animals↗
PubMed1980

The effect of temperature on capacitance changes in an oscillating model membrane.

The electrical properties of model membranes are altered during stretching or pressure pulses. We have used a mechanico-electric transduction model to interpret the temperature dependence of capacitance changes produced in oxidized cholesterol membranes during mechanical oscillation. The relative contribution of the torus and bilayor portions of the membrane to the capacitance change is identified. The difference in elasticity between the bilayer and torus decreases rapidly with decreasing temperature and ultimately the torus becomes as solid as the bilayer portion of the model membrane.

Calorimetry, Differential Scanning↗