The effect of dexamethasone on the radiation survival response and misonidazole-induced hypoxic-cell cytotoxicity in Chinese hamster cells V-79–753Bin vitro

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Abstract
Overnight exposure of Chinese hamster V-79-753B cells [lung fibroblast] to microgram quantities of the synthetic corticosteroid dexamethasone resulted in a decrease in sensitivity towards radiation, both in air and in hypoxia. The effect was dose-modifying and the oxygen enhancement ratio did not change appreciably. When dexamethasone-treated hypoxic cells were irradiated in the presence of misonidazole, a hypoxic cell radiosensitizer [used in cancer therapy], there was a decrease in radiation sensitivity compared with untreated hypoxic cells irradiated with misonidazole. The effect of dexamethasone cannot be attributed to classical radioprotection since administration of the drug immediately or 4.5 h before irradiation did not alter the survival response of hypoxic cells with or without misonidazole. Neither can this increased radioresistance be attributed to synchronization to a more resistant phase of the cell cycle since pretreated cells remained more radioresistant for at least 6 h after the removal of the drug. Evidently, dexamethasone induces metabolic changes in cells which alter their radiosensitivity. Whatever metabolic changes may occur there was no effect on the uptake of 14C-misonidazole into dexamethasone-treated or control cells. There was a pronounced decrease in hypoxic-cell cytotoxicity induced by misonidazole in cells pretreated with dexamethasone. The implications of these results are discussed.