INAIL, Department of Occupational Medicine, Epidemiology and Hygiene, Monte Porzio Catone, Rome Italy.
Department of Environmental Biology, NMR Based Metabolomics Laboratory, Sapienza University of Rome, Rome Italy.
Toxicol Lett. 2020 Aug 1;328:28-34. doi: 10.1016/j.toxlet.2020.03.022. Epub 2020 Apr 16.
Occupational exposure to hyperbaric atmosphere occurs in workers who carry out their activity in environments where breathing air pressure is at least 10% higher than pressure at sea level, and operations can be divided in Dry or Wet activities. The increased air pressure implies the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), consumption of antioxidants and reduction of antioxidant enzyme activity, causing lipid peroxidation, DNA and RNA damage. The present study was aimed to establish the relation between hyperbaric exposure and metabolic changes due to ROS unbalance, by means of the determination of urinary biomarkers of oxidatively generated damage to DNA and RNA during a controlled diving session. The investigated biomarkers were 8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). The experimental session involved six experienced divers subjected to 3 atmospheres absolute for 30 minutes in two different experiments, in both dry and wet conditions. Urine samples were collected at t = 0 (before exposure) and 30 (end of exposure),90, 240, 480 and 720 minutes. The concentration of 8-oxoGua, 8-oxoGuo, and 8-oxodGuo was determined by isotopic dilution high performance liquid chromatography (HPLC-MS/MS). In all subjects there is an increase of the urinary excretion of 8oxo-Guo and 8oxo-dGuo, in both conditions, after 1.5 - 4 hours from the start of the experiment, and that the values tend to return to the baseline after 12 hours. Besides that, also the nucleic magnetic resonance (NMR)-based untargeted metabolomics was employed for the same objective on the same samples, confirming a different metabolic response in the subjects exposed to dry or wet conditions. In particular, the observed hypoxanthine urinary level increases during the underwater hyperbaric exposure, in agreement with the trend observed for 8-oxoGuo and 8-oxodGuo levels. Present results confirmed the relationship between exposure and oxidative stress and depicted a clear temporal trend of the investigated biomarkers. Due to the possible negative consequences of oxidative stress on workers, present research shows a new line in term of risk prevention.
职业性暴露于高压环境发生在那些在气压至少比海平面高 10%的环境中工作的人员中，操作可分为干式或湿式活动。增加的气压意味着活性氧（ROS）和活性氮（RNS）的形成，抗氧化剂的消耗和抗氧化酶活性的降低，导致脂质过氧化，DNA 和 RNA 损伤。本研究旨在通过在受控潜水过程中测定尿液中 DNA 和 RNA 氧化生成损伤的生物标志物，确定高压暴露与由于 ROS 失衡引起的代谢变化之间的关系。所研究的生物标志物为 8-氧代-7,8-二氢鸟嘌呤（8-氧代鸟嘌呤），8-氧代-7,8-二氢鸟苷（8-氧代鸟苷）和 8-氧代-7,8-二脱氧鸟苷（8-氧代 dGuo）。实验分为两个不同的实验，每个实验有 6 名经验丰富的潜水员在 3 个大气压下暴露 30 分钟，在干式和湿式条件下进行。在 t = 0（暴露前）和 30（暴露结束），90，240，480 和 720 分钟时采集尿样。通过同位素稀释高效液相色谱（HPLC-MS/MS）测定 8-氧代鸟嘌呤，8-氧代鸟苷和 8-氧代 dGuo 的浓度。在所有受试者中，在实验开始后 1.5-4 小时，两种条件下的 8oxo-Guo 和 8oxo-dGuo 的尿排泄均增加，并且在 12 小时后，这些值趋于恢复到基线。除此之外，还对相同的样本进行了基于核酸磁共振（NMR）的非靶向代谢组学，以同样的目的证实了在干式或湿式条件下暴露的受试者的不同代谢反应。特别是，在水下高压暴露期间观察到黄嘌呤的尿液水平增加，与 8-氧代鸟苷和 8-氧代 dGuo 水平的趋势一致。目前的结果证实了暴露与氧化应激之间的关系，并描绘了所研究生物标志物的清晰时间趋势。由于氧化应激对工人可能产生的负面影响，本研究在预防风险方面开辟了一条新途径。
