Cell killing and the sequencing of hyperthermia and radiation.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to W C Dewey.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The effect of 0.05 M and 1.5 M NaCl treatments on CHO cells during and after irradiation has been examined. Treatment with either hypotonic or hypertonic salt solutions during and after irradiation resulted in the fixation of radiation damage which would otherwise not be expressed. The half time for fixation was 4 to 5 min, and the increased expression of the potentially lethal damage by anisotonic solutions was mainly characterized by large decreases in the shoulder of the survival curve, as well as by decreases in DO. Fixation of radiation damage at 37 degrees C occurred to a much greater extent for the hypertonic treatment than for the hypotonic treatment and was greater at 37 degrees C than at 20 degrees C. Although both the hypotonic and hypertonic treatments during and after irradiation reduced or eliminated the repair of sublethal and potentially lethal damage, treatment during irradiation only, radiosensitized the cells when the treatment was hypotonic, and radioprotected the cells when the treatment was hypertonic. These observations are discussed in relation to salt treatments and different temperatures altering competition between repair and fixation of potentially lethal lesions, the number of which depends on the particular salt treatment at the time of irradiation.
The response of cultured CHO cells to U.V.L. irradiation during treatment with anisotonic solutions shows that treatment with hypotonic sucrose, NaCl or KCl solutions causes an increase in the cellular U.V.L. sensitivity, while exposure to hypertonic solutions causes a large decrease in U.V.L. sensitivity. Cells exposed to 1.8 M sucrose, NaCl or KCl solutions and given a U.V.L. dose of 252 erg/mm2 towards the end of the 20 min solution exposure time have survival levels which are respectively 228,26, and 23 times higher than the controls, i.e. cells irradiated in phosphate buffered saline. Cell volume data obtained using a Coulter counter, and nuclear area data of attached cells obtained using an optical microscope with a micrometer reticle, show that cell and nuclear size are related to U.V.L. sensitivity. That is, as cells shrink and the nuclear area decreases, the cells become more U.V.L.-resistant. During hypotonic treatment with 0.1 M NaCl, the cell volume, nuclear area and U.V.L. sensitivity increased in the first 2 to 4 min of exposure time, but at longer exposure times (greater than 3 to 4 min), cell volume, nuclear area and cellular U.V.L. sensitivity decreased. For 0.1 M KCl treatment the cells initially displayed a rapid increase in volume, nuclear area and U.V.L. sensitivity, but at the longer exposure times no decrease in cell and nuclear size were observed, and a slight increase in U.V.L. sensitivity occurred. Changes in U.V.L. sensitivity were related to changes in nuclear size and cell volume; however, calculations showed that during hypertonic treatment there is an ionic effect as well as an osmotic effect. That is, the cellular U.V.L. survival in equal hypertonic concentrations of NaCl or KCl was lower than in the same concentration of sucrose.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The mitotic cells from an asynchronous population of Chinese hamster ovary cells exposed to 41.5 degrees for 7 hr were examined by light and electron microscopy to determine if there were any morphological abnormalities related to cell death or lengthening of metaphase induced by hyperthermia. All components of the mitotic apparatus were formed during exposure to heat, and the mitotic apparatus was functional as demonstrated by eventual cell division. However, heat caused the nuclear envelope to reform precociously around the chromosomes except in the region of the kinetochores, and the nuclear envelope remained associated with the chromatids during segregation. The precocious reformation of the nuclear envelope may be responsible for the lengthening of metaphase. Cells undergoing mitosis during the heat treatment possessed large evaginations of the plasma membrane, and the ubiquitous cortical microfilaments were absent in the region of these evaginations. Possibly related to the membrane damage were osmotic changes resulting in swollen mitochondria observed in heated cells entering mitosis. Since hyperthermic damage to the plasma membrane-microfilament complex was not observed in interphase cells or in cells completing division but was morphologically expressed during mitosis, the thermal lability of the plasma membrane must increase as the cells enter mitosis.
Recommendations are made for hyperthermia research to be carried out at the molecular, cellular, and animal levels. Effects of heat alone should be distinguished from effects of heat combined with radiation or chemotherapy. Factors to be considered include tumor cell environment, treatment sequencing, thermal tolerance, cell kinetics, any possible nonthermal effects, and therapeutic gain.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Chinese hamster ovary cells were synchronized without inhibitors by mitotic selection and labelled in G1, S or G2 phase by incubation for 90 min with [3H]- OR [14C]uridine. Purified polyribosomes were extracted with phenol and the polyadenylated mRNA prepared by poly(U)-Sepharose chromatography. Poly-adenylated [3H]uridine-labelled mRNA from the G1 phase of the cell cycle was compared by exponential polyacrylamide gel electrophoresis in formamide with [14C] uridine-labelled polyadenylated nRNA from the S or G2 phase. The electrophoretic patterns obtained correspond to the size range expected for mRNA (7-28 S). No prominent differences were detected between mRNAs synthesized in different phases of the cell cycle. From these data we conclude that the major size classes of polyribosomal poly(A)-containing mRNA are synthesized in equal ratios throughout the cell cycle.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.