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I V Chapman

Publications and source records attributed to I V Chapman.

At least 19 recordsLinked to original sources
PubMed2003

The influence of depleted glutathione levels on the photodynamic action of zinc phthalocyanine in CHO K1 cells.

OBJECTIVE: The current study focuses on any influence that depletion of endogenous glutathione in CHO K1 cells may have on the photodynamic action of zinc phthalocyanine (ZnPc). MATERIALS AND METHODS: Two lasers--a HeNe laser, 632.5 nm, maximum power output 3.5 mW, and a Toshiba semiconducting laser, 670 nm, maximum power of 7 mW--were used. Chinese Hamster Ovary cells (CHO K1) were exposed to light, 2-10 J. Cellular reduced glutathione levels [GSH] were depressed prior to exposure to ZnPc and laser light, using buthionine sulphoximine, a potent inhibitor of gamma-glutamylcysteine synthetase. The influence of hypoxic intracellular conditions was studied by reduction of oxygen content of cells by 80% following purging of cell cultures with nitrogen. RESULTS: In well-aerated cells, doubling times are reduced by the photodynamic action of ZnPc by 29 +/- 6%, fig 2 (p = 0.01). Cells with lowered [GSH] do not show this effect (p = 0.1). When hypoxic cells are studied at normal [GSH], no photodynamic effect is observed (p = 0.1). When cell viability is studied, using the 670-nm laser, a photodynamic effect is observed, (80% fall from controls, p < 0.001), irrespective of the cellular [GSH] level for a single dose of 6 J. This effect is observed in cells with normal [GSH], for varied doses of 2 J and higher (63% fall at 2 J, p < 0.001). CONCLUSIONS: Lowered [GSH] was observed to depress the photodynamic effect of ZnPc when cell-doubling times were the endpoint. The photostimulating effect of ZnPc was similarly suppressed by hypoxic conditions. When cell viability was the endpoint, then a photodynamic effect of ZnPc was observed irrespective of the endogenous [GSH] values.

Animals↗
PubMed1993

The effect of fenclofenac on the regeneration of lymphocytes in rats following total body irradiation.

The effect of fenclofenac on the regeneration of white blood cells in Sprague-Dawley rats following total body irradiation was investigated. The lowest dose of total body irradiation that would suppress the peripheral blood lymphocyte count by at least 50% was found to be 1.0 Gray in a preliminary experiment. Fenclofenac in a dose of 150 mg/kg/day retarded the regeneration of lymphocytes following total body irradiation of 1 Gray: this effect was also seen in the CD4, CD8 and B-lymphocyte subsets. This suppressive effect in vivo may be due to interference with replicative growth of white blood cells since previous in vitro experiments have shown suppression of lymphocyte growth at a stage later than activation in the cell cycle. The suppressive effects on leucocyte regeneration in vivo suggest that fenclofenac may have promise as an immunosuppressive drug with fewer serious side effects than the currently available immunosuppressive drugs.

Animals↗
PubMed1993

Thermal properties and fluidity of human erythrocyte membranes in diabetes mellitus.

Exposure of human erythrocytes to elevated temperatures induces a decrease in stability of the cell membrane. Thermally induced haemolysis of erythrocytes from patients with type 1 diabetes and from healthy control individuals was measured as a function of duration of exposure to heat between 48.0 and 54.0 degrees C. Results indicate that the thermosensitivity of erythrocytes from patients with type 1 diabetes is lower than for control individuals. Activation energies for lysis were similar for both control and 'diabetic' erythrocytes, being 298.3 and 287.7 kJ/mol, respectively. The steady-state fluorescence anisotropy measurement of TMA-DPH for each step of haemolysis was employed as a parameter characterizing membrane fluidity. We found that 'diabetic' erythrocyte membranes had significantly decreased fluidity. The relationship between fluidity and rate of haemolysis indicates that the rate-limiting step in the haemolysis reaction involves the rupturing of the membrane bilayer.

Diabetes Mellitus, Type 1↗
PubMed1985

Influence of ethidium bromide on hyperthermic modification of bleomycin-DNA interaction.

The effect of hyperthermic treatment on the binding of 59Fe-labeled bleomycin to DNA has been studied. Enhanced binding was observed at elevated temperatures. The influence of the DNA-intercalating agent, ethidium bromide, on bleomycin-DNA interaction was also studied and revealed a considerable decrease in this interaction at ethidium bromide levels below 1 microgram/ml. Ethidium bromide was observed to remove the enhanced bleomycin-DNA interaction recorded previously following incubation at hyperthermic temperatures. Synergistic action of bleomycin and hyperthermia on loss of clonogenic ability of HT29R cells is reported. Incubation of cells under hyperthermic conditions with bleomycin in the presence of ethidium bromide removes this synergism, producing a less than additive effect for the action of bleomycin and heat after ethidium bromide effects are taken into account.

Adenocarcinoma↗
PubMed1983

Thermal enhancement of bleomycin-induced tumour growth delay: the effect of dose fractionation.

The influence of hyperthermia on bleomycin-induced growth delay of a syngeneic murine carcinoma has been studied in both simultaneous and sequential schedules for single and multi-fraction drug dose. The results reveal thermal potentiation of drug-induced growth delay if treatment is given simultaneously. This observed potentiation is independent of single or multi-fraction drug administration. Sequential pre-heating treatment resulted in only additive growth rate depression for single and two-fraction drug doses. However, when the drug dose was given in three fractions a significant thermal potentiation was observed for both simultaneous and sequential schedules.

Animals↗
PubMed1983

Hyperthermic modification of bleomycin--DNA interaction detected by electron spin resonance.

Electron spin resonance spectra of DNA labeled with each of four spin-labeling compounds have been studied to detect interaction between the antibiotic bleomycin and DNA. Only one of these labels, compound IV, resulted in a modified spectrum when bound to DNA and the latter was subjected to bleomycin. This property has been used to monitor DNA-bleomycin interactions under physiological and hyperthermic conditions. Bleomycin produced an increase in rotational correlation time of the residue bound to DNA at 37 degrees C and a significantly higher increase at 43 degrees C. Some effect was still detected with bleomycin at 37 degrees C after preheating at 43 degrees C. Parallel studies have revealed enhanced binding of 59Fe-bleomycin to DNA during and after hyperthermic treatment.

Bleomycin↗
PubMed1982

Effect of hyperthermia and ionizing radiation on the erythrocyte membrane.

Spin-label studies of the effects of hyperthermia on the erythrocyte membrane revealed a decrease in the fluidity of lipids and changes in the state of membrane proteins. The rate of haemolysis in iso-osmotic glycerol solution was increased. Changes of most of the parameters studied when plotted in Arrhenius coordinates revealed a discontinuity (critical hyperthermic transition in the membrane) between 46 and 50 degrees C. Studies of the combined action of ionizing radiation (100 Gy) and hyperthermia (43 degrees C) showed the same direction of changes for (Na-K-Mg)-ATPase activity and spectra of membrane-bound maleimide spin label for both agents, but the additivity of changes depended on the parameter studied.

Animals↗
PubMed1981

Diffusion kinetics of tritiated uridine into HeLa cells previously exposed to hyperthermia.

Hyperthermic treatment of HeLa cells at 42 degrees C for 60 min depressed the specific activity of these cells when incubated with 3H-uridine both during and post heating compared to cells maintained at 37 degrees C. These changes were unlikely to arise from increased leakage from the cells and may partially be attributed to membrane damage influencing facilitated diffusion. Diffusion kinetic data for incorporation of the radiolabel into the T.C.A. soluble and T.C.A. insoluble fractions of HeLa cells indicated that a significant depression of Vmax and a significant elevation of Km for incorporation of 3H UdR into RNA may possibly result from an isotope dilution effect attributed to degrading pre-ribosomal RNA under the effect of hyperthermia.

Diffusion↗
PubMed1981

beta-Thromboglobulin levels in plasma of jaundiced neonates exposed to phototherapy.

It has been suggested that changes take place in human platelets when they are exposed to fluorescent light of 10.8W/m2/sec at 460 nm. Loss of ability to aggregate and increase in turnover rate have been reported. However, studies of the effect of fluorescent light on adult platelets when exposed to the level of irradiance used clinically (3.5W/m2/sec) for 60 min did not reveal this effect. A study was therefore designed to compare the effects of bilirubin and phototherapy alone and in combination on cord and adult blood platelets obtained from jaundiced neonates. Using beta-thromboglobulin as the indicator of platelet damage, no significant change was found in platelet poor plasma from cord or adult blood following exposure to bilirubin and/or light, nor was any change found in the plasma of jaundiced neonates before and after therapy. Although the duration of exposure to light in this study was short, the results suggest that the lower levels of irradiance used clinically are not harmful to platelets and that the results of studies done with three times as much irradiance have little clinical relevance.

Beta-Globulins↗
PubMed1980

Modification of ultrasound induced changes in mammalian cells by increased viscosity of medium and increased ambient pressure.

Ehrlich ascites tumour cells (E.A.T.) in suspension were exposed to ultrasound of frequency 1x5 MHZ, intensities 1x4, 2x8 W/cm2 for 60 min at 37 degrees C. The suspensions of E.A.T. cells were contained in Perspex vessels with Melinex windows, situated in the near field of a piezoceramic transducer. Subsequently the rate of net influx of Rb-86 ions was studied over a period of 90 min. A reduced Rb-86 activity of insonated cell populations was observed compared to controls. Similar experiments were carried out involving E.A.T. cells suspended in isotonic medium containing 0x25 per cent agar (2x1 centipoise). No significant depression of uptake of Rb-86 ions was observed at 2x8 W/cm2, 1x5 MHZ. Cells insonated in normal medium at 1x9 atmos. helium pressure subsequently showed no depression of Rb-86 uptake, compared to controls, following insonation at 2x8 W/cm2, 1x5 MHZ for 60 min.

Animals↗
PubMed1977

Combined effects of bleomycin and X-rays on DNA synthesis in asynchronous Ehrlich ascites cells in suspension.

Separate and combined effects of bleomycin and X-rays on rates of uptake of [14C]thymidine into Ehrlich ascites cells were assessed for extracellular drug concentrations of 12 micron (20 microgram/ml) and radiation doses of 2-5 krad. Rates of DNA synthesis were followed by monitoring the activity of the acid-insoluble portion of the asynchronous culture. The 14C activity of the acid-soluble pool was assessed in determining the rate of passage of 14C-TdR across the cell membrane. The results reveal that whilst the effects of each agent on TdR uptake rates are markedly different, they both inhibit DNA synthesis. Combined studies with both agents, 2-5 krad X-rays plus 20 microgram/ml bleomycin before, simultaneously or after exposure to X-rays, produced additive or less than additive effects on rates of incorporation of TdR into DNA. However, when the drug dose is split 2 X 10 microgram/ml before and after exposure to 2-5 krad X-rays, a synergistic effect on inhibition of DNA synthesis is observed.

Animals↗
PubMed1977

The effects of X-radiation on thymidine-transport kinetics and DNA synthesis in Ehrlich ascites tumour cells in relation to extracellular thymidine concentration.

A TdR carrier-transport system, believed to be facilitated diffusion, has been shown to exist in Ehrlich ascites tumour cells. It is suggested that this system is the predominant transport mechanism at low extracellular concentrations (less than 1-5 micron). The transport system was damaged considerably by 5 krad X-radiation, resulting in a 30-35 per cent reduction in the initial total TdR uptake rat at low extracellular concentrations and 15-20 min after irradiation. The extent of the damage was dependent on the age of the cells as was reflected by relative decreases in V max and Km. It can be concluded that the enhanced depression in 14C-TdR incorporation into DNA of irradiated cells when low precursor concentrations were used for monitoring, is partly attributed to the radiation-induced damage to the carrier-transport system. The permeability constant for passive diffusion in asynchronous E.A.T. cells and the endogenous natural rate of dTTP synthesis in S-phase cells were estimated.

Animals↗
PubMed1975

Radiation-induced decrease in influx rates of potassium ions into thymocytes in vitro in relation to decreased intracellular adenosine triphosphate concentrations.

The relationship between decreases in the adenosine triphosphate content of irradiated thymocytes and observed changes in the influx constant values for potassium ions in the same cells have been investigated. The results suggest that radiation-reduced ATP concentrations may be a rate-limiting factor controlling the active transport of potassium, 3--4 hours after X-irradiation in the range 2--20 krad. However, over the first hour of incubation, post-exposure ATP levels have not decreased sufficiently to be a major factor in the observed decrease in active uptake of potassium ions. This evidence is supported by comparisons of the influence of 1 mM adenine on radiation-reduced ATP levels and influx constants over the first hour after irradiation.

Adenosine Triphosphate↗