Department of Toxicology and Carcinogeneis, Nofer Institute of Occupational Medicine, Lodz, Poland.
Mutat Res. 2012 Mar 1;731(1-2):58-63. doi: 10.1016/j.mrfmmm.2011.10.010. Epub 2011 Nov 4.
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.
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.
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.
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.
职业性接触氧化亚氮（N2O）和/或卤代烃已被认为会导致遗传物质损伤，但潜在机制尚不清楚。本研究调查了氧化过程在与麻醉废气接触相关的遗传毒性中的作用。
该研究在 36 名女性护士和 36 名年龄和工作年限相匹配的未接触女性医护人员中进行。通过使用能够评估氧化 DNA 损伤的形式嘧啶糖苷酶（FPG）修饰的彗星试验来检测遗传毒性效应。通过用 2'，7'-二氯荧光素二乙酸酯进行荧光光谱法来研究白细胞中的活性氧（ROS）。通过免疫或比色法测量包括 8-异前列腺素 F2α（8-iso-PGF2α）、硫代巴比妥酸反应物质（TBARS）、α-生育酚和谷胱甘肽过氧化物酶（GPX）活性在内的氧化应激标志物。通过气相色谱和质谱监测 N2O、七氟醚和异氟醚。
该研究首次记录了环境空气中 N2O 水平与氧化 DNA 损伤之间的正相关关系。相比之下，未观察到遗传毒性效应与七氟醚或异氟醚之间存在关联。此外，接触麻醉废气的护士的 ROS 生成以及血浆和尿液中的 TBARS 和 8-iso-PGF2α 浓度分别升高，而 GPX 活性降低。路径分析表明，N2O 暴露、氧化应激和 DNA 损伤之间存在因果关系。
职业性接触 N2O 与氧化 DNA 损伤增加有关，暴露水平在这方面起着关键作用。氧化应激增加可能代表慢性 N2O 暴露与遗传毒性之间的机制联系。
