Protection against misonidazole-induced toxicity in vitro by non-steroidal anti-inflammatory agents

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Abstract

Overnight exposure of Chinese hamster cells, V-79–753B, to certain non-steroidal anti-inflammatory agents (NSAIA) including indomethacin (5 × 10−5M), benoxaprofen (5 × 10−5M) or aspirin (10−4M) protected against misonidazoleinduced toxicity both in air and in hypoxia at 37°C. In no instance was the radiosensitivity of cells affected by these treatments nor was there any effect on the amount of acute hypoxic cell radiosensitization produced by 1.0 mM misonidazole. There was no protection against misonidazole-induced toxicity when cells were pretreated with theophylline (10−3M). Protection against misonidazole-induced toxicity by benoxaprofen was not reversed by the addition of 1 μg/ml prostaglandin E1 or F. The results are discussed in terms of possible mechanisms.

Keywords

Non-steroidal anti-inflammatory agents
Misonidazole
Benoxaprofen
Aspirin
Indomethacin

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Misonidazole was kindly supplied by Roche Products (Welwyn Garden City, Herts, England). Benoxaprofen was a gift from Eli Lilly (Windelsham, Surrey, England). Aspirin, indomethacin, prostaglandin E1 and F and theophylline were obtained from the Sigma Chemical Co. (Poole, Dorset, England).

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