Roles of thiols in cellular radiosensitivity.

Cellular thiols appear to have two separable mechanisms for influencing cellular radiosensitivity: 1) a direct role, through radical scavenging and/or hydrogen donation processes, and 2) an indirect role, regulating the amount of oxygen (or other electron affinic sensitizer) able to reach the radiosensitive targets of the cell. The contribution of each is easily measured with multicell spheroids, using fluorescence activated cell sorting techniques for selective recovery of cells from any depth within spheroids (i.e., from areas with different oxygenation). We have found that the region in the spheroid over which the transition from aerobic to anoxic conditions occurs is highly dependent on cellular thiol levels. Combining thiol depletion by DL-buthionine-S, R-sulfoximine (BSO) and electron affinic radiosensitization using misonidazole resulted in a markedly potentiated response to radiation, which we interpret as being primarily a result of reoxygenation.