Alkylating and oxidative stresses in smoking and non-smoking patients with COPD: Implications for lung carcinogenesis.
Alkylating and oxidative stresses in smoking and non-smoking patients with COPD: Implications for lung carcinogenesis.
复制标题
DOI：
10.1016/j.freeradbiomed.2020.12.442
复制
发表时间：
2021-02-20
影响因子：
7.4
通讯作者：
Hu CW
中科院分区：
文献类型：
--
作者：
Shih YM;Chang YJ;Cooke MS;Pan CH;Hu CH;Chao MR;Hu CW
慢性阻塞性肺疾病（COPD）是一种以慢性炎症和不可逆气道阻塞为特征的疾病。吸烟是发展COPD的主要危险因素。众所周知，COPD也与患肺癌的风险增加密切相关。香烟烟雾含有高浓度的氧化剂和各种致癌物（例如，烟草衍生的亚硝胺），其可引起氧化和烷基化应激，这也可由炎症引起。然而，令人惊讶的是，除了氧化应激外，关于COPD患者的烷基化应激负担和烟草衍生致癌物的解毒效率的信息很少。在这项研究中，我们使用LC-MS/MS来测量典型的烟草特异性致癌物4-（甲基亚硝胺）-1-（3-吡啶基）-1-丁酮（NNK），其主要代谢产物，4-（甲基亚硝胺）-1-（3-吡啶基）-1-丁醇（NNAL），氧化应激的三种生物标志物（8-oxo-7，8-dihydroguanine，8-oxoGua; 8-oxo-7，8-dihydro-2'-deoxyguanosine，8-oxodGuo; 8-oxo-7，8-dihydroguanosine，8-oxoGuo）和两种烷化剂应激的生物标志物（N7-甲基鸟嘌呤，N7-MeGua和N3-甲基腺嘌呤，N3-米德），在吸烟和非吸烟COPD患者和健康对照的尿液中。我们的研究结果表明，不仅是氧化应激显着升高的COPD患者相比，对照组，但也烷化应激。值得注意的是，烷基化应激水平（即，N7-MeGua）与COPD严重程度高度相关，而不受年龄和吸烟状况的影响。此外，COPD吸烟者的游离NNAL与总NNAL的比率显著高于对照吸烟者，这意味着COPD吸烟者中NNK的解毒效率较低。这一比例在3-4期COPD吸烟者中甚至高于1-2期COPD吸烟者。总之，我们的结果表明，烟草衍生的致癌物（例如，NNK）与COPD的发病机制和可能的进展有关。除了氧化应激，慢性炎症引起的烷基化应激似乎也是COPD患者的主要因素。
Chronic obstructive pulmonary disease (COPD) is a disease characterized by chronic inflammation and irreversible airway obstruction. Cigarette smoking is the predominant risk factor for developing COPD. It is well-known that the COPD is also strongly associated with an increased risk of developing lung cancer. Cigarette smoke contains elevated concentrations of oxidants and various carcinogens (e.g., tobacco-derived nitrosamines) that can cause oxidative and alkylating stresses, which can also arise from inflammation. However, it is surprising that, except for oxidative stress, little information is available on the burden of alkylating stress and the detoxification efficiency of tobacco-derived carcinogens in COPD patients. In this study, we used LC-MS/MS to measure the archetypical tobacco-specific carcinogenic 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), three biomarkers of oxidative stress (8-oxo-7,8-dihydroguanine, 8-oxoGua; 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodGuo; 8-oxo-7,8-dihydroguanosine, 8-oxoGuo) and two biomarkers of alkylating stress (N7-methylguanine, N7-MeGua and N3-methyladenine, N3-MeAde), in the urine of smoking and non-smoking COPD patients and healthy controls. Our results showed that not only was oxidative stress significantly elevated in the COPD patients compared to the controls, but also alkylating stress. Significantly, levels of alkylating stress (i.e., N7-MeGua) were highly correlated with the COPD severity and not affected by age and smoking status. Furthermore, COPD smokers had significantly higher ratios of free NNAL to the total NNAL than control smokers, implying a lower detoxification efficiency of NNK in COPD smokers. This ratio was even higher in COPD smokers with stages 3-4 than in COPD smokers with stages 1-2. Taken together, our results demonstrated that the detoxification efficiency of tobacco-derived carcinogens (e.g., NNK) was associated with the pathogenesis and possibly the progression of COPD. In addition to oxidative stress, alkylating stress derived from chronic inflammation appears to be also dominant in COPD patients.
登录
查看更多内容
影响因子：
3.9
作者：
McGuinness AJ;Sapey E
通讯作者：
Sapey E
DOI：
10.1016/j.lungcan.2015.08.017
发表时间：
2015-11
期刊：
Lung cancer (Amsterdam, Netherlands)
影响因子：
--
作者：
Durham AL;Adcock IM
通讯作者：
Adcock IM
影响因子：
9.6
作者：
Carr, Laurie L.;Jacobson, Sean;Bowler, Russell P.
通讯作者：
Bowler, Russell P.
DOI：
10.1038/nrc3185
发表时间：
2012-01-12
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1164/ajrccm.162.2.9908132
发表时间：
2000-08-01
影响因子：
24.7
作者：
Ichinose, M;Sugiura, H;Shirato, K
通讯作者：
Shirato, K