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Biomedical subjects

G P Raaphorst

Publications and source records attributed to G P Raaphorst.

At least 109 records · Page 6Linked to original sources
PubMed1984

Thermal enhancement of radiosensitivity in normal and ataxia telangiectasia human cells.

Normal human and ataxia telangiectasia (AT) fibroblasts were tested for enhancement of radiosensitivity by hyperthermia. In normal fibroblasts, thermal enhancement of radiosensitivity occurred at 42.0 degrees C and 45.0 degrees C and was greatest for simultaneous treatments of heat and radiation. This thermal enhancement decreased, as an incubation time at 37.0 degrees C was introduced either between heat and X-ray, or X-ray and heat, treatments. AT cells were more radiosensitive (D0 = 0.67 Gy) than normal cells (D0 = 1.4 Gy). Heating at 42.0 degrees or 45.0 degrees C resulted in enhanced radiosensitivity, which was equal for heating before, during or after irradiation. These data show that normal human fibroblasts can recover from heat and radiation treatments, while AT fibroblasts lack this ability.

Ataxia Telangiectasia↗
PubMed1984

Inhibition of DMSO-induced differentiation by hyperthermia in a murine erythroleukemia cell system.

Friend erythroleukemia cells were induced by dimethyl sulfoxide (DMSO) into erythroid differentiation, as characterized by the production of hemoglobin. Induction increased with DMSO concentrations up to 1.5% v/v, at which point about 90% of the cell population produced hemoglobin as measured by a benzidine-staining technique. Heat treatment at 39.0-40.5 degrees C during a 7-day-incubation period, for differentiation in the presence of DMSO, resulted in the inhibition of hemoglobin induction. Also, acute heat treatments at 41.5-46.0 degrees C before or after the addition of DMSO resulted in the inhibition of DMSO induction. This effect was greatest when DMSO was present during heating. The results support the conclusion that hyperthermia inhibits the differentiation process which is induced by DMSO treatment.

Animals↗
PubMed1984

Effects of oxygen and misonidazole on cell transformation and cell killing in C3H 10T1/2 cells by X rays in vitro.

The effects of oxygen (air) and misonidazole on the transformation and killing of 10T1/2 cells by X rays were examined. The oxygen effect for the cell transformation end point was very similar to that for cell killing. Misonidazole enhanced both cell killing and cell transformation to a similar extent. The enhancement of both end points by misonidazole occurred only in the absence of oxygen during irradiation and was of lesser magnitude than that observed for oxygen. These results demonstrate that the radiation chemical processes leading to cell killing and cell transformation, respectively, are affected similarly by these two enhancers of radiation action.

Aerobiosis↗
PubMed1984

Modification by anisotonic treatment of repair and fixation of radiation damage in cell killing and transformation.

Anisotonic treatment of V79 cells after irradiation resulted in extensive fixation of potentially lethal damage (PLD). Fixation of PLD occurred more rapidly when treated with 1.5 mol l-1 NaCl than with 0.05 mol l-1 NaCl. These effects were further enhanced when cells were held at 0 degree C instead of 37 degrees C during irradiation. When the X-ray (10.0 Gy) and salt treatments were separated by incubation at 37 degrees C, survival increased rapidly by a factor of 2000, while repair of PLD in cells held in a plateau phase after X-rays (10.0 Gy) caused survival to increase four-fold. The data indicate that these mammalian cells sustain and repair a much larger amount of PLD than is measured by the conventional method of holding cells in a non-progressing state after irradiation. Radiation sensitivity in cells was modified by BrdUrd incorporation into cellular DNA or exposure to DMSO during irradiation. For these cells, fixation of damage by post-irradiation anisotonic treatment proceeded at the same rate for BrdUrd-treated cells, and at a diminished rate for DMSO-treated cells, compared with cells irradiated in the absence of these compounds. In C3H-10T 1/2 cells, post-irradiation anisotonic treatment (with 0.05 or 1.5 mol l-1 NaCl) also resulted in fixation of PLD and a rapid recovery when the X-ray and salt treatments were separated by incubation at 37 degrees C. Treatment with 0.05 or 1.5 mol l-1 NaCl solutions immediately after irradiation also resulted in elevated transformation frequencies, which increased with exposure time to anisotonic solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Thermal sensitivity and radiosensitization in V79 cells after BrdUrd or IdUrd incorporation.

Chinese hamster V79 cells were exposed to 10(-5) moles/liter bromodeoxyuridine (BrdUrd) or iododeoxyuridine (IdUrd) for 16 or 29 hr and then tested for thermal sensitivity, radiosensitivity, and sensitivity to the combined treatments of heat and radiation. BrdUrd and IdUrd treatment of cells resulted in enhanced radiosensitivity which increased with exposure time but had little or no effect on thermal sensitivity. For 42.0 degrees C heating, no effect was observed, while for 45.0 degrees C heating, a small decrease in thermal sensitivity occurred for both 16- and 29-hr exposure times, in the combined treatment of heat and radiation, the presence of BrdUrd or IdUrd resulted in about the same thermal enhancement in radiosensitivity. BrdUrd and IdUrd uptake into cellular DNA were measured using high-pressure liquid chromatography and, after a 29-hr exposure to 10(-5) moles/liter of BrdUrd or IdUrd, approximately 40% of the thymidine was substituted.

Acclimatization↗
PubMed1983

Thermal radiosensitization in Chinese hamster (V79) and mouse C3H 10T 1/2 cells. The thermotolerance effect.

The sensitivity of V79 cells and normal or morphologically transformed C3H-10T 1/2 cells to X-rays, heat or heat plus X-rays was examined. The normal and transformed C3H-10T 1/2 cell lines were equally sensitive to heat at 42.0 degrees C and radiation. The V79 cells were more heat sensitive. Thermal radiosensitization occurred for all 3 cell lines for the combined heat and radiation treatments and was greatest for simultaneous treatment. Recovery occurred when the treatments were separated by an incubation interval at 37 degrees C. For the V79 cells, recovery was much greater for X-rays preceding heat compared to X-rays following heat. This difference was not as great in the C3H-10T 1/2 cell lines. The transformed C3H-10T 1/2 cells were more sensitive compared to the normal for the simultaneous treatment or for heating followed by irradiation. For prolonged heating at 42.0 degrees C, after which thermotolerance occurred in all 3 cell lines, the radiosensitivity still increased as a function of heating time even though no additional cell killing occurred from the heat treatment alone. For heating V79 cells at 41.0 degrees C no further increase in radiosensitivity occurred, as cells became thermotolerant during prolonged heating. Also for the development of thermotolerance during incubation at 37 degrees C between two heat treatments, thermal radiosensitization decreased demonstrating that thermotolerance can affect radiosensitization by hyperthermia.

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

Hyperthermia in a differentiating murine erythroleukemia cell line: cell killing by heat and radiation.

The survival response of Friend erythroleukemia cells (a differentiating cell system) to heat and radiation has been examined. The Friend erythroleukemia cells (FELC) were more heat and radiation sensitive than V79 cells, and the heat and radiation survival curves possessed shoulders, showing the ability of the cells to accumulate sublethal damage. Thermal tolerance was expressed after prolonged heating at 41.0-42.0 degrees C. Thermal radiosensitization by heating at 42.0 or 45.0 degrees C was greatest for simultaneous heat and radiation treatments, and recovery occurred when the cells were incubated at 37 degrees C between the heat and radiation or radiation and heat treatments. Arrhenius analysis of the FELC heat survival data showed that the curve for thermal inactivation possessed a break at about 43.0 degrees C and that the thermal inactivation energies above and below the break point were comparable to those for V79 cells and other cell lines reported in the literature.

Animals↗
PubMed1983

Hyperthermia in a differentiating murine erythroleukaemia cell line: II. Effect of heat on haem induction by radiation.

Friend erythroleukaemia cells (FELC) were induced to a haem-producing state by X-rays. The percentage of haem positive cells was maximum for doses between 10 and 15 Gy. Heat treatment at 42.0 degrees C or 45.0 degrees C during or after irradiation inhibited haem induction whereas heating before irradiation enhanced it. Incubation at 37 degrees C between heating and irradiation resulted in a decline in induction levels, indicating repair of heat damage that interacts with X-ray damage. Incubation at 37 degrees C between irradiation and heating did not result in changed haem induction levels, indicating a lack of repair of radiation damage that could interact with subsequent damage produced by heating.

Animals↗
PubMed1983

A comparison of cell killing by heat and/or X rays in Chinese hamster V79 cells, Friend erythroleukemia mouse cells, and human thymocyte MOLT-4 cells.

The radiation and/or heat sensitivity of Chinese hamster V79 cells, Friend erythroleukemia (FELC) mouse cells, and MOLT-4 human transformed thymocytes were compared. MOLT-4 cells were more radiosensitive (D0 = 0.50 Gy) than FELC (D0 = 0.65 Gy) and V79 cells (D0 = 1.43 Gy). Arrhenius analysis showed that MOLT-4 cells were more heat sensitive than FELC or V79 cells below 42.0 degrees C, but more heat resistant at higher temperatures. In addition, the MOLT-4 cells showed a single-heat inactivation energy between 41.0 and 45.0 degrees C, while FELC and V79 cells both showed a transition in the inactivation energy at about 43.0 and 43.5 degrees C, respectively. These differences may be related to the fact that the upper temperature limit for the development of thermal tolerance during continuous heating was lower for MOLT-4 cells than for FELC or V79 cells. Killing of FELC and V79 cells was dependent on the sequence in which heat and X rays were applied, but the greatest effect was obtained when both treatments were given simultaneously. Recovery occurred when treatments were separated by incubation at 37.0 degrees C. The MOLT-4 cells did not show a sequence dependence for heating and irradiation. Survival of MOLT-4 cells after heating and/or irradiation was compared using trypan blue dye exclusion or colony formation. Both assays showed similar qualitative responses, but survival levels measured by the trypan blue assay were much higher than those determined from the colony-forming assay.

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↗
PubMed1983

Hyperthermia and thermal tolerance in normal and ataxia telangiectasia human cell strains.

Three normal human fibroblast strains, two human ataxia telangiectasia heterozygote cell strains, and two human ataxia telangiectasia homozygote cell strains were studied for their thermal responses between 41.0 and 46.0 degrees. The heat sensitivities of all cell strains were comparable, and all cell strains were relatively heat resistant compared to Chinese hamster cells. Both normal and ataxia telangiectasia human cells developed thermal tolerance during heating at temperatures less than or equal to 43 degrees and during incubation at 37 degrees after acute heating at 45.0 degrees. For survival measured down to the 5 to 10% level, heat survival curves for all seven human cell strains lacked shoulders, indicating the inability of such cells to accumulate sublethal heat damage. Analysis of the cell survival curve data by the method of Arrhenius showed that the thermal inactivation energies for human cells were 127 and 230 kcal/mol above and below the break at 43.5 degrees, respectively, and are about the same as for Chinese hamster cells and other animal cells, implying similar mechanisms of heat inactivation.

Animals↗
PubMed1982

The effect of chronic and acute heat conditioning on the development of thermal tolerance.

Survival studies with Chinese hamster ovary cells showed that thermal tolerance, which developed during chronic heating (treatment times greater than or equal to 1 hr) or after acute heating (treatment times less than 1 hr) involves similar mechanisms. For example, cells that expressed thermal tolerance during a 6-14 hr chronic heat treatment at 41.5 degrees C or 42 degrees C also expressed thermal tolerance to a subsequent acute treatment at 45.5 degrees C. Also, cells heated acutely for 10 min at 45.5 degrees C and incubated at 37 degrees C for 12 hr showed tolerance to both 45.5 degrees C acute and 42 degrees C chronic hyperthermia. Finally, thermal tolerance developed between fractionated acute heat treatment at 45.5 degrees C and fractionated chronic heat treatments at 42.5 degrees C. These data indicate that when cells are tolerant to chronic hyperthermia they are also tolerant to acute hyperthermia and that the reverse is also true.

Adaptation, Physiological↗
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↗