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.
Sölen
G
G
Department of Tumor Biology II, Karolinska Institute, Stockholm, Sweden.
Edgren
M
M
Scott
O C
OC
Révész
L
L
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D004229:Dithiothreitol / Q000494:pharmacology*; D004347:Drug Interactions; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D066298:In Vitro Techniques; D008954:Models, Biological; D010100:Oxygen / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents; D010100:Oxygen; D004229:Dithiothreitol