Oxidative DNA damage and oxidative stress in subjects occupationally exposed to nitrous oxide (N2O)

Objectives: Occupational exposure to nitrous oxide (N2O) and/or halogenated hydrocarbons has been suggested to induce damage of genetic material, but the underlying mechanisms remain obscure. This study investigated the role of oxidative processes in the genotoxicity associated with exposure to waste anaesthetic gases. Methods: The study was performed in 36 female nurses and in 36 unexposed female health care workers matched for age and employment duration. Genotoxic effects were examined by Comet test modification employing formamidopyrimidine glycosylase (FPG) that allows assessment of oxidative DNA damage. Reactive oxygen species (ROS) in leukocytes were investigated by fluorescence spectroscopy with 2',7'-dichlorofluorescin diacetate. Oxidative stress markers including 8-iso-prostaglandin F-2 alpha (8-iso-PGF(2 alpha) thiobarbituric acid-reacive substances (TBARS), alpha-tocopherol, and glutathione peroxidise (GPX) activity were measured immuno- or colorimetrically. N2O, sevoflurane and isoflurane were monitored by gas chromatography and mass spectrometry. Results: The study documents for the first time the positive correlation between the oxidative DNA damage and the N2O levels in the ambient air. By contrast, no association was observed between genotoxic effects and sevoflurane or isoflurane. In addition, ROS generation and plasma and urine concentrations of TBARS and 8-iso-PGF(2 alpha) respectively, were elevated, while GPX activity was reduced in nurses exposed to waste anaesthetic gases. Path analysis pointed to a causal relationship between N2O exposure, oxidative stress and DNA damage. Conclusion: Occupational exposure to N2O is associated with increased oxidative DNA damage and the level of exposure plays a critical role in this regard. Increased oxidative stress may represent a mechanistic link between chronic N2O exposure and genotoxicity. (C) 2011 Elsevier B.V. All rights reserved.