Glutathione-reactive nitro compounds as radiosensitizers: mechanistic and therapeutic implications.

The "extra" radiosensitization seen with GSH-reactive nitro compounds is too large to be accounted for by GSH-depletion acting independently--there must be competition. The GS-conjugate leaks out of cells slowly and is trapped at high concentrations. Its properties, such as concentration trapped and reduction potential, must be considered. Limited therapeutic exploitation of the glutathione conjugate trapping and concomitant GSH depletion may be possible if intratumor injection is permitted.