Chen Zhihai, Wang Dapeng, Liu Xing, Pei Weiwei, Li Jianxiang, Cao Yi, Zhang Jie, An Yan, Nie Jihua, Tong Jian
Department of Toxicology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, 215123, Suzhou, China.
Environ Health Prev Med. 2015 Sep;20(5):318-24. doi: 10.1007/s12199-015-0469-z. Epub 2015 May 13.
Reactive oxygen species (ROS) induced by exogenous toxicants are suggested to be involved in carcinogenesis by oxidative modification of DNA. 8-Hydroxyl-2-deoxyguanosine (8-OHdG) has been considered as a reliable biomarker for oxidative DNA damage both in vivo and in vitro studies. But the effect of smoking on oxidative damage has not yet been fully elucidated.
Wistar rats were exposed to cigarette smoke at concentrations of 20 and 60 % for 30 min, twice/day for 45 weeks. Then the histopathology of lung tissues, levels of ROS, 8-OHdG, and total antioxidant (T-AOC), expression of DNA repair enzymes, e.g. 8-oxyguaine DNA glycosylase (OGG1), and MutThomolog 1 (Oxidized Purine Nucleoside Triphosphatase, MTH1) were determined in urine, peripheral blood lymphocytes, and lung tissue.
The results showed that long-term cigarette smoke exposure can cause obvious damages of lung tissue in rats. In addition, a significant and cigarette smoke concentration-dependent increase in ROS and 8-OHdG were observed compared with the non-exposed control rats. In contrast, the expression of OGG1 and MTH1, and T-AOC levels were obviously decreased after long-term exposure to cigarette smoke.
These findings indicate that long-term exposure to cigarette smoker increases ROS levels, decreases total antioxidant capacity, and interferes DNA repair capacity that eventually induces oxidative DNA damage, which appears to play an important role in cigarette smoke-induced lung injury in rats, and determination of 8-OHdG levels might be a useful method for monitoring oxidative damage in cigarette smokers.
外源性毒物诱导产生的活性氧（ROS）被认为可通过对DNA的氧化修饰参与致癌过程。在体内和体外研究中，8-羟基-2'-脱氧鸟苷（8-OHdG）一直被视为氧化DNA损伤的可靠生物标志物。但吸烟对氧化损伤的影响尚未完全阐明。
将Wistar大鼠暴露于浓度为20%和60%的香烟烟雾中30分钟，每天两次，持续45周。然后测定肺组织的组织病理学、ROS、8-OHdG和总抗氧化剂（T-AOC）水平，以及尿液、外周血淋巴细胞和肺组织中DNA修复酶（如8-氧代鸟嘌呤DNA糖基化酶（OGG1）和MutT同源物1（氧化嘌呤核苷三磷酸酶，MTH1））的表达。
结果表明，长期暴露于香烟烟雾可导致大鼠肺组织明显损伤。此外，与未暴露的对照大鼠相比，观察到ROS和8-OHdG显著且呈香烟烟雾浓度依赖性增加。相反，长期暴露于香烟烟雾后，OGG1和MTH1的表达以及T-AOC水平明显降低。
这些发现表明，长期接触香烟烟雾会增加ROS水平，降低总抗氧化能力，并干扰DNA修复能力，最终导致氧化DNA损伤，这似乎在香烟烟雾诱导的大鼠肺损伤中起重要作用，并且测定8-OHdG水平可能是监测吸烟者氧化损伤的一种有用方法。
