Radioprotective Effect of N-acetylcysteine in Vitro Using the Induction of DNA Breaks as End-point

Abstract

Cultures of Chinese hamster cells were treated with N-acetylcysteine (NAC) and irradiated under hypoxic or aerobic conditions. Protection factors (PFs) were calculated using the yield of DNA breaks as a measure of the radiation response. With NAC up to 50 mmol dm⁻³, the PF values were smaller for aerobically- than for hypoxically-irradiated cells. In contrast with NAC concentrations > 100 mmol dm⁻³, the PF values for aerobically-irradiated cells were larger than those for hypoxic cells. This reversal is in agreement with the predictions of a modified competition model, the ‘X-model’. The value of X (the ratio of reparable to non-reparable damage) was calculated to be close to 5 for the NAC-treated cells, i.e. about 18% of the radiation damage was not reparable. The increase of the total non-protein bound thiols (NPSH) and GSH content after NAC treatment was measured both in whole cells and isolated nuclei. Measurement of the cellular NPSH content showed a continuous increase with increasing NAC concentrations in the medium, independent of treatment time. In contrast, the amount of intracellular and intranuclear GSH increased with prolonged incubation time with NAC. No quantitative relationship was found between PF values and cellular NPSH or GSH content.