title: Oxidative DNA damage and oxidative stress in subjects occupationally exposed to nitrous oxide (N(2)O).
abstract: OBJECTIVE
  Occupational exposure to nitrous oxide (N(2)O) 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(2α) (8-iso-PGF(2α)), thiobarbituric acid-reacive substances (TBARS), α-tocopherol, and glutathione peroxidise (GPX) activity were measured immuno- or colorimetrically. N(2)O, 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 N(2)O 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(2α), respectively, were elevated, while GPX activity was reduced in nurses exposed to waste anaesthetic gases. Path analysis pointed to a causal relationship between N(2)O exposure, oxidative stress and DNA damage.
  
  
  CONCLUSIONS
  Occupational exposure to N(2)O 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 N(2)O exposure and genotoxicity.
authors.affiliation: Department of Toxicology and Carcinogeneis, Nofer Institute of Occupational Medicine, Lodz, Poland. tewono@imp.lodz.pl
authors.forename: Teresa
authors.initials: T
authors.lastname: Wrońska-Nofer
authors.forename: Jerzy-Roch
authors.initials: JR
authors.lastname: Nofer
authors.forename: Jolanta
authors.initials: J
authors.lastname: Jajte
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Dziubałtowska
authors.forename: Wiesław
authors.initials: W
authors.lastname: Szymczak
authors.forename: Wojciech
authors.initials: W
authors.lastname: Krajewski
authors.forename: Wojciech
authors.initials: W
authors.lastname: Wąsowicz
authors.forename: Konrad
authors.initials: K
authors.lastname: Rydzyński
mesh_terms: D000395:Air Pollutants, Occupational / Q000633:toxicity*; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D016022:Case-Control Studies; D020552:Comet Assay; D004249:DNA Damage; D005260:Female; D006282:Health Personnel; D006801:Humans; D009154:Mutation; D009609:Nitrous Oxide / Q000633:toxicity*; D009741:Nursing Staff, Hospital; D016273:Occupational Exposure / Q000009:adverse effects*; D018384:Oxidative Stress
chemical_list: D000395:Air Pollutants, Occupational; D018685:Anesthetics, Inhalation; D009609:Nitrous Oxide