Alkylating and oxidative stresses in smoking and non-smoking patients with COPD: Implications for lung carcinogenesis
| Autor: | Chih-Hong Pan, Chiung-Wen Hu, Yuan-Jhe Chang, Ching-Hsuan Hu, Mu-Rong Chao, Ying-Ming Shih, Marcus S. Cooke |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Nitrosamines Carcinogenesis Inflammation medicine.disease_cause Biochemistry Gastroenterology Article Pathogenesis 03 medical and health sciences Pulmonary Disease Chronic Obstructive 0302 clinical medicine Tandem Mass Spectrometry Physiology (medical) Internal medicine Medicine Humans Risk factor Lung cancer Lung Carcinogen COPD business.industry medicine.disease respiratory tract diseases Oxidative Stress 030104 developmental biology medicine.anatomical_structure Carcinogens medicine.symptom business 030217 neurology & neurosurgery Oxidative stress Chromatography Liquid |
| Zdroj: | Free Radic Biol Med |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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