The role of N-acetylcysteine as a putative radioprotective agent on X-ray-induced DNA damage as evaluated by alkaline single-cell gel electrophoresis.

Samples of human whole blood from 8 different donors were incubated with physiological saline or N-acetyl-L-cysteine (NAC, 1 x 10(-3) M) before being irradiated in vitro with high-energy X-rays (0.7 or 2.0 Gy). Primary DNA damage was evaluated in isolated lymphocytes using alkaline single-cell gel electrophoresis. Whereas the lymphocytes from non-irradiated blood samples showed a similar 'background level' of damage, there was a difference in sensitivity towards the radiation-induced DNA damage, especially at 2.0 Gy. When the data were pooled there was a clear and dose-related increase (p < 0.001) in damage, both in the absence and presence of NAC. Using the two most sensitive 'comet parameters' for DNA damage, i.e., the tail inertia and tail moment, the radiation-induced damage was found to be significantly increased already at 0.7 Gy in the samples that had been irradiated without NAC. Overall, NAC was found to be without radioprotective effects. Instead, the incubation with NAC itself was found to be associated with a slightly increased level of DNA damage. If the present findings are relevant also in an in vivo situation using peripheral lymphocytes as a surrogate for non-malignant cells in the body, NAC seems to be of limited value as a radioprotective agent in the clinic, at least when it comes to the acute DNA-damaging effects of therapeutic doses of high-energy X-rays.