Radiosensitization of Anoxic Cells of E. Coli K-12 by Organic Nitroxyl Free Radicals

Summary

Radiosensitization of anoxic, log-phase cells of E. coli K-12, strain AB 2463 rec⁻A, by organic nitroxyl free radicals has been studied by means of two kinds of rapid-mixing equipment.

For the sensitizer concentrations used (10⁻³ M) the nitroxyl-mediated radiosensitization is shown to be nearly independent of the dose-rate from 20 rads/sec to 8 × 10⁹ rads/sec. Insignificant sensitization was observed when cells were irradiated, and at various times t afterwards (where t > 10 m sec), mixed with an unirradiated solution of nitroxyls.

The time course of the nitroxyl-mediated radiosensitization resulting from irradiation performed at given times after mixing of the cell suspension with the nitroxyl solution was determined. It suggests that three processes are involved:

(1) A very rapid one, perhaps associated with membrane transients, which for 10⁻³ sec < t < 10⁻¹ sec provides a small sensitization (about 30 per cent increase).

(2) An intermediate process, perhaps governed by diffusion of nitroxyls into the cells. Within about 5 sec this process increases the radiosensitivity by a factor of 3 relative to that of anoxic cells in the absence of nitroxyls.

(3) A slow process, which, in addition to diffusion, may reflect reactions of nitroxyls with (unirradiated) cellular constituents, among which endogenous sulphydryls may be involved. This process requires times of several minutes for completion.