PubMed HealthSearch

Biomedical subjects

O C Scott

Publications and source records attributed to O C Scott.

17 recordsLinked to original sources

Radioprotection by dithiothreitol (DTT) at varying oxygen concentrations: predictions of a modified competition model and theory evaluation.

Cultures of Chinese hamster cells were treated with dithiothreitol (DTT) at varying concentrations, and exposed to radiation aerobically or at various oxygen tensions. The extent of radioprotection by DTT was calculated using the yield of DNA strand breaks as a measure of the radiation response. The curve of protection factors (PF) had a specific pattern, characterized by low PF values at low and high oxygen tensions with a peak at an intermediate tension. The peak value of the PF was increased and shifted to higher oxygen tensions as DTT concentrations increased. The experimentally observed pattern of the PF curves is incompatible with the Alper model of the competition hypothesis, which assumes that the entire radiation injury can be modified by sensitizers or protectors. On the other hand, the pattern is consistent with a model (X model) which is based upon a modification of the original hypothesis and assumes two types of radiation injury, only one of which is modifiable.

Animals

Radiosensitization by oxygen and radioprotection by thiols: analysis of the combined action according to a modified competition model.

Cultures of Chinese hamster fibroblasts were treated with dithiothreitol (DTT) and irradiated under aerobic or hypoxic conditions. Protection factors (PF) and oxygen enhancement ratios (OER) were calculated with DNA breakage as the criterion of the radiation effects, and related to the intracellular concentration of non-protein-bound thiols (NPSH). When the increment of the cellular NPSH was in a low concentration range, the PF values were smaller for aerobically than for hypoxically irradiated cells. In contrast, in the case of cells with a large increase in NPSH concentration, the PF values for the hypoxically irradiated cells were smaller. As a consequence the PF curve of the hypoxically and aerobically exposed cells crossed, and OER values followed a bell-shaped curve with respect to increasing cellular NPSH concentrations. The observations could be explained by assuming a competition between the damage-restituting and damage-fixing reactants, and postulating that only a certain proportion of the damaged targets is reparable.

Animals

Cellular glutathione content and K values. II.

After exposure to radiation in the presence of different oxygen concentrations, the OER values were determined for human fibroblasts cell strains with differing intrinsic GSH content, and cells depleted of GSH to different extent by treatment with BSO. The yield of DNA single-strand breaks was used as the measure of radiosensitivity. The K values were found to be related specifically to the GSH concentration in the cell nuclei. A good agreement was found between the experimental observations and the prediction of a variant of the competition model in which a second type of damage, not influenced by oxygen, was included.

DNA Damage

Cellular glutathione content and K values.

The K values for two cell strains with differing intrinsic GSH concentrations have been measured with the yield of DNA breaks as end-point of the radiation effect. The K value of the strain with reduced GSH content was decreased (1.59 microM O2) in comparison to the K value (3.01 microM O2) for the strain with a normal GSH content. The significance of the observation is discussed in relation to competition models. All variants of the competition model agree in predicting a reduction of K, if GSH is reduced.

Cells

Combined effect of misonidazole and glutathione depletion by buthionine sulphoximine on cellular radiation response.

Chinese hamster cells (V79) and glutathione-proficient (GSH+/+) and glutathione-deficient (GSH-/-) human fibroblasts were treated with a glutathione (GSH)-depleting agent buthionine sulphoximine (BSO) and the hypoxic radiosensitizer misonidazole (MISO), separately or in combination. Subsequently, the cells were exposed to X-rays. Determination of the yield of single-strand DNA breaks (ssb) immediately after irradiation indicated no effect of BSO or MISO treatment when radiation exposure was made aerobically. Assuming that ssb determined immediately after irradiation reflects mainly the effect of radical processes, the results obtained with BSO and MISO, singly and in combination, agreed well with the predictions of a modified version of the 'competition model' using V79 and GSH+/+ cells. Some results obtained with GSH-/- cells could not be so explained.

Animals