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 wi th physiological saline or N-acetyl-L-cysteine (NAC, 1 x 10(-3) M) bef ore being irradiated in vitro with high-energy X-rays (0.7 or 2.0 Gy). Primary DNA damage was evaluated in isolated lymphocytes using alkali ne single-cell gel electrophoresis. Whereas the lymphocytes from non-i rradiated blood samples showed a similar 'background level' of damage, there was a difference in sensitivity towards the radiation-induced D NA 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 ab sence and presence of NAC. Using the two most sensitive 'comet paramet ers' for DNA damage, i.e., the tail inertia and tail moment, the radia tion-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 incu bation with NAC itself was found to be associated with a slightly incr eased level of DNA damage. If the present findings are relevant also i n 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 a cute DNA-damaging effects of therapeutic doses of high-energy X-rays.