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Biomedical subjects

G P Raaphorst

Publications and source records attributed to G P Raaphorst.

At least 145 records · Page 8Linked to original sources
PubMed1978

The radiation response of cultured mammalian V79-S171 cells exposed to a wide concentration range of sulphate salt solutions.

The radiation response of Chinese hamster cells (V79) exposed to a wide concentration range of Li2SO4, Na2SO4 or K2SO4 has been examined and compared with the radiation response of cells treated in an identical manner with LiCl, NaCl, or KCl solutions. At hypotonic salt concentrations, cells were radiosensitized by both the chloride and sulphate salts. At high salt concentrations, approximately greater than 0.9 M, a radioprotective effect was observed with both chloride and sulphate salts. At intermediate salt concentrations from about 0.2 to 0.9 M, the cells that were treated with the sulphate salt solutions were radioprotected; cells treated with chloride salt solutions were radiosensitized. The difference in radiation response was attributed to the difference in anions for the two types of salts used.

Animals↗
PubMed1978

Effect of salt solutions on the radiosensitivity of mammalian cells. IV. Treatment with NaCl solutions containing ouabain, NEM, PNAP, cysteamine or DMSO.

The effects of a wide concentration range of NaCl solutions containing either ouabain, ethanol, para-nitroacetophenone (PNAP), N-ethylmaleimide (NEM), cysteamine or dimethyl sulphoxide (DMSO) on cellular radiosensitivity have been examined. Ouabain and NEM treatment increased the radiosensitivity of V79 Chinese hamster cells, but the action of these chemicals did not depend on the concentration of NaCl. PNAP increased cellular radiosensitivity with increasing NaCl concentration reaching a maximum effect at 0.6 to 0.7 M NaCl. The radioprotective properties of cysteamine, DMSO and ethanol were all strongly dependent on the NaCl concentration in a complex but qualitatively similar manner. DMSO (2.0 M) increased radiation survival of cells after a 1380 rad dose by a factor of about 10(4) when present in 0.075 M NaCl and by a factor of 8.7 when present in 1.2 M NaCl.

Acetophenones↗
PubMed1978

Water content and spin lattice relaxation times of cultured mammalian cells subjected to various salt, sucrose, or DMSO solutions.

The proton spin lattice relaxation time (T1) of mammalian cells subjected to a wide range of salt, sucrose, or DMSO solutions has been measured and minima in the T1 curves for cells treated with all solutes except DMSO were observed. At hypotonic solute concentrations, the increases observed in T1 of the cell sample could be correlated to an increase in the amount of intracellular water. At high solute concentrations, cells shrink losing intracellular water; yet increases in T1 were observed. The increases were attributed to changes in macromolecular conformation resulting in changes in the coordination shells associated with the macromolecules. Since these effects are also observed with sucrose, the basic phenomenon is concluded to be due to osmotic factors. However, ion specific effects were also observed. When protein was dissolved in a wide range of NaCl or KCl solutions, the minimum in the T1 curve was not observed, demonstrating that the effect must be characteristic of the response of intact cells to the various solutions.

Body Fluids↗
PubMed1977

Effect of salt solutions on radiosensitivity of mammalian cells. I. Specific ion effects.

The radiation isodose survival curve of cells subjected to a wide concentration range of sucrose solutions has two maxima separated by a minimum. Both cations and anions can alter the cellular radiosensitivity above and beyond the osmotic effect observed for cells treated with sucrose solutions. The basic shape of the isodose curve can also be modulated by changes in temperature and solution exposure times. Some of these alterations in radiosensitivity may be related to changes in the amount and structure of cellular water or macromolecular conformation or to the direct effect of the ions, expecially at high solute concentrations.

Acetates↗
PubMed1977

Effect of salt solutions on radiosensitivity of mammalian cells. II. Treatment with hypotonic solutions.

Chinese hamster (V79) cells were treated with hypotonic NaCl, NaCl-ouabain, KCl, LiCl, NH4Cl, NaNO3 or sucrose solutions and irradiated at various times during exposure to the solution. The extreme increase in the radiosensitivity of these cells, mainly characterized by changes in DO, could be attributed to increases in the cell water-content and possibly the decrease in total cell water structure. The various ions may exert their specific effects on radiosensitivity by influencing the above water-related factors.

Ammonium Chloride↗
PubMed1977

Effect of salt solutions on radiosensitivity of mammalian cells. III. Treatment with hypertonic solutions.

V79 Chinese hamster cells were treated with hypertonic solutions of NaCl or KCl and irradiated rat various times before, during, or after exposure to the solution. In solutions of molarities between 0-2 and 0-5 M, the cellular radiosensitivity increases with the molarity of the bathing solution. At these molarities, the hypertonic solution need not be present during irradiation to sensitize cells. Furthermore, radiosensitivity of cells could be increased by exposing cells for longer times to the hypertonic solution before irradiation. At higher salt concentrations (at 1-5 to 1-8 M), significant radioprotection is observed. Survival curve data showed that this protection was characterized by an increase in DO and a decrease in n, while the survival curves of cells sensitized with 0-465 M NaCl or with lower concentrations exhibited mainly changes in DO. The 1-55 M NaCl solution must be present during radiation to give a protective effect. Prolonged exposure to the salt before irradiation reduced the amount of radioprotection afforded by the salt. The results are discussed in terms of the effects of ions on histones, cellular water structure and the cell-aging cycle.

Cell Survival↗
PubMed1976

Survival of unprotected, mammalian plateau-phase cells following freezing in liquid nitrogen.

Unprotected, mammalian cells in plateau phase are at least a factor of four times more sensitive to freeze-thaw damage than exponential-phase cells. The former suffer about 15-20% more sublethal damage after one freeze-thaw cycle than the latter and repair this damage more slowly. Exposure of plateau-phase cells to freeze-thaw damage lengthens the time required to traverse the cell cycle in the exposed generation. These cells may more closely represent the state in tissues than exponential-phase populations.

Animals↗
PubMedDate not supplied

[In vitro radiosensitivity of skin fibroblasts can identify a group of patients with complications in various health tissues after radiotherapy].

PURPOSE: A retrospective study of the in vitro radiosensitivity of skin fibroblasts derived from two groups of patients treated by definitive radiotherapy for a variety of tumors who either displayed or did not display severe complications. PATIENTS AND METHODS: Seven radiotherapy patients were selected: three were treated for head and neck, prostate and non-Hodgkin lymphoma tumors, and did not develop any significant complications (control group); four patients were treated for bladder, thyroid, head and neck and anal canal tumors and developed serious acute and especially late reactions (hypersensitive group). Primary cell cultures of skin fibroblasts were established and their radiosensitivity studied by the clonogenic assay after exposing to single radiation doses ranging between 1 and 8 Gy. RESULTS: The survival fraction at 2 Gy (SF2) ranged from 0.27 to 0.38, with a mean of 0.33 for the control group, and from 0.10 to 0.20 with a mean of 0.17 for the hypersensitive group. The Mann-Whitney non-parametric test showed that the difference between the two means was statistically significant (p = 0.03). CONCLUSION: The data are in favor of a correlation between the radiosensitivity of patients' fibroblasts and the reactions of different normal tissues to radiotherapy. This association supports the use of the clonogenic survival, or a surrogate test, as a predictive assay. The multiplicity of normal tissues and organs implicated in this association suggests the existence of genetic factors that determine, at least in part, the radiosensitivity of target cells involved in the expression of normal tissues complications following radiotherapy.

Aged↗
PubMedDate not supplied

Response to pulsed dose rate irradiation with and without mild hyperthermia using tumour and normal cell lines.

To determine whether pulsed dose rate irradiation in combination with mild hyperthermia could radiosensitize cells in comparison to pulsed dose rate irradiation alone, human ovarian carcinoma (A2780s, cisplatin- and radiation-sensitive, and A2780cp, cisplatin- and radiation-resistant) and human fibroblast (AG1522) cell lines were used. Cells were irradiated in vitro using two fraction sizes, 0.53 Gy given every hour and 1.6 Gy given every 3h, with an overall average dose rate of 0.53 Gy/h. The data showed that 40 degrees C hyperthermia did not radiosensitize any of the cell lines for the 0.53 Gy every 1 h fractionation scheme. In addition, mild hyperthermia radiosensitized both carcinoma cell lines when using the 1.6 Gy fraction size for all doses tested in the A2780s and at higher doses in the A2780cp, but not the normal cell line. These results suggest a potential clinical advantage when using the 1.6 Gy fraction size with 40 degrees C mild hyperthermia, since hyperthermia radiosensitized the carcinoma cells but not the normal cells.

Antineoplastic Agents↗
PubMedDate not supplied

Comparison of response to radiation, hyperthermia and cisplatin in parental and polymerase beta knockout cells.

The role of polymerase beta in response to radiation, cisplatin and hyperthermia was examined in a pair of mouse cell lines, comprising a normal parental line and a derivative with polymerase beta knockout. Cell survival was assessed using the colony survival assay. For irradiation, there was no difference in response between the two cell lines. Treatment with cisplatin for 1 h showed a large increase in resistance in the mutant cell line. The results with hyperthermia were more complex. The mutant was more resistant to 45 degrees C heating, but was slightly more heat sensitive than the wild type at 41 degrees C. Thus, in summary, while the knockout of polymerase beta did not alter radiation sensitivity, it did increase resistance to cisplatin and induced resistance to hyperthermia at higher temperatures (45 degrees C).

Animals↗
PubMedDate not supplied

Thermal radiosensitization and repair inhibition in human melanoma cells: a comparison of survival and DNA double strand breaks.

Human melanoma cells (SK-mel-3) were treated with combinations of radiation and hyperthermia treatment and survival (using the colony forming assay) and DNA double strand breaks (dsb's) (using pulsed field gel electrophoresis) were measured for immediate and delayed plating. The cells were treated in plateau phase, so that delayed plating would result in repair of potentially lethal damage (PLD). Delayed plating showed PLDR for both the survival and the dsb end-point. One hour of heating after irradiation showed a temperature dependent increase in radiosensitization for both the survival endpoint and the dsb endpoint for the temperature range from 42 to 45 degrees C. One hour of heating at 43 degrees C after irradiation resulted in the partial inhibition of PLDR and recovery of dsb's. For heating at 45 degrees C the inhibition of dsb repair was complete. There was good correlation between the survival endpoint and the dsb endpoint for the thermal radiosensitization for both the immediate plating and the PLDR protocols. These data indicate that hyperthermia inhibition of repair of PLD is probably due to the inhibition of dsb rejoining. These correlations were made at the same dose levels for survival and dsb analysis, thus avoiding the potential complications of many earlier studies which used much higher doses for dsb analysis than for survival studies.

DNA Damage↗
PubMedDate not supplied

On the spatial resolution of clinical thermometers.

In this work the spatial resolution of type T (copper-Constantan) and type K (Chromel-Alumel) multipoint thermocouple thermometers was investigated. For clinical use, thermocouples are usually inserted within catheters to provide easy access, reproducibility, and a sterile environment. The effect of several types of catheter on the ability of these thermometers to accurately resolve thermal gradients was studied. The influence of the number of wire pairs within the multipoint thermometer was also investigated. A mathematical model has been developed to determine the spatial resolving power of these thermometers. Results indicate that type K thermocouples are generally superior to type T and the use of catheters plays a significant role in spatial resolution. Moreover, the use of mineral oil as a thermal coupling agent between the catheter and the thermometer was also found to have some effect.

Humans↗
PubMedDate not supplied

A safe method of analysis for mechanical damage in spherical radioactive sources used in remote afterloading brachytherapy devices.

The examination of brachytherapy sources in a quality assurance program can result in significant exposure to staff. Even though exposure may be within prescribed limits attempts should be made to reduce such exposure to as low as reasonably achievable (ALARA concept). In this report, a system that can be used to examine small spherical radiation sources while minimizing exposure to staff is described.

Brachytherapy↗
PubMedDate not supplied

The influence of ionic environment on the thermal response of cultured mammalian cells.

Chinese hamster cells exposed to monovalent or divalent ionic solutions were sensitized to hyperthermia treatment. Thermosensitization was dependent on the type of cationic salt. Divalent salt solutions caused greater sensitization than monovalent salt solutions. The addition of glucose or the reduction of pH in the salt solutions did not alter thermosensitivity.

Animals↗
PubMedDate not supplied

Normal cells and malignant cells transfected with the HRas oncogene have the same heat sensitivity in culture.

Mouse embryo cells (C3H 10T1/2) were transfected with a plasmid (pAL8A) containing the HRas oncogene and neomycin resistance gene. Five transfected cell clones were isolated and established as cell lines, and these showed neomycin resistance. Two of these cell lines expressed a normal morphology while three showed a transformed morphology. Four of the cell lines produced tumours in nude mice. Flow cytometry measurements showed that exponentially growing cell cultures of the five transfected cell lines had the same cell cycle distribution as the normal parental cell line. The sensitivity to hyperthermia of the five transfected cell lines was the same as that of the normal cell line for temperatures ranging from 42.0 to 45.0 degrees C. Thus in these studies we found no difference in the thermal sensitivity of normal and malignant cells transfected by the Hras oncogene.

Cell Line↗
PubMedDate not supplied

Evaluation of thermoradiosensitization and transformation in C3H-10T1/2 cells induced into a thermotolerant state.

C3H-10T1/2 cells were induced to a thermotolerant state by heating at 41.0 degrees C, 42.0 degrees C, 45.0 degrees C or by treatment with ethanol. As thermotolerance developed, cellular heat sensitivity and thermoradiosensitization decreased. Transformation was measured by scoring transformed foci as previously described (Raaphorst et al. 1986 a). Hyperthermia alone in normal and thermotolerant cells did not increase the transformation frequency above background levels. The level of transformation induced by irradiation increased up to three-fold as cells became thermotolerant. This was observed for thermotolerance induced by long-term heating at 41.0 degrees C or short acute heat treatments at 42.0 degrees C or 45.0 degrees C followed by incubation at 37.0 degrees C. Treatment with ethanol also induced thermotolerance, and reduced radiosensitization and increased transformation in the thermotolerant state.

Adaptation, Physiological↗
PubMedDate not supplied

Hyperthermia enhancement of radiation response and inhibition of recovery from radiation damage in human glioma cells.

Three human glioma cell lines were tested for the effectiveness of hyperthermia and thermal radiosensitization. Thermal sensitization was evaluated from the perspective of increased radiosensitivity as well as inhibition of recovery from radiation damage. The three glioma cell lines tested showed large shoulders on the radiation survival curve and a large capacity for recovery of potentially lethal radiation damage. Hyperthermia caused radiosensitization in all three cell lines, which was primarily characterized by the reduction of the survival curve shoulder with moderate decreases in the survival curve slope. The radiosensitization was dependent on the time and temperature of the hyperthermia treatment. At 45 degree C for 60 min the shoulder of the radiation survival curve could be completely eliminated and the degree of enhanced cell killing at the 2 Gy level ranged from factors of 10 to 20 under the various conditions. When hyperthermia was given to cells which were irradiated and then plated immediately, or delayed for 8 h before plating to allow recovery, hyperthermia was found to cause radiosensitization under both conditions. In addition, when the hyperthermia dose was increased the difference between the immediate plating and the delayed plating survival curve decreased and for 45 degrees C for 60 min this difference was completely eliminated, concomitantly with the elimination of the survival curve shoulder. These data indicate that hyperthermia may play a role in radiosensitization for the treatment of human glioma.

Brain Neoplasms↗