The Role of Thiols in Response to Radiation and Drugs

Glutathione (GSH) has been implicated as the major intracellular nonprotein thiol involved in protecting hypoxic cells against radiation injury (1–10). In contrast, we have demonstrated increased radiosensitivity for GSH-depleted aerobic and hypoxic A549 human lung carcinoma cells (2–5). This parallel increase in radiosensitivity conflicts with the popular interpretation of existing data regarding the effect of GSH depletion on hypoxic sensitivity alone (5). Subsequently, ratios of (hypoxic slope) / (aerobic slope) may be misleading if GSH depletion alters both responses, but by different mechanisms.