Combined Radiation-Protective and Radiation-Sensitizing Agents: II. Radiosensitivity of Hypoxic or Aerobic Chinese Hamster Fibroblasts in the Presence of Cysteamine and Misonidazole: Implications for the "Oxygen Effect" (With Appendix on Calculation of Dose-Modifying Factors)

Abstract

Experiments have been done to test whether a hypoxic cell radiosensitizing agent (misonidazole) can be combined with a radioprotecting agent (cysteamine) to equalize partially the radiation response of hypoxic and aerobic mammalian cells in tissue culture. The results indicate that cysteamine will protect against the radiosensitization of a hypoxic cell sensitizing drug (2.5 mM misonidazole) at much lower concentration than it will protect against the radiosensitization of oxygen (350 ..mu..M). Thus the addition of a radiation-protective drug tends to cancel the drug benefit of the radiosensitizer and therefore increases the differential response of hypoxic and aerobic cells rather than equalizing this response. The data suggest that even in situations where tumor tissue absorbs far less radioprotective drug than normal tissue (e.g., WR 2721), one might expect difficulties with the simultaneous administration of radiosensitizing and radioprotecting drugs.