Skip to main content
Top
Published in: World Journal of Surgical Oncology 1/2013

Open Access 01-12-2013 | Research

Detection of reactive oxygen metabolites in malignant and adjacent normal tissues of patients with lung cancer

Authors: Hacer Kuzu Okur, Meral Yuksel, Tunc Lacin, Volkan Baysungur, Erdal Okur

Published in: World Journal of Surgical Oncology | Issue 1/2013

Login to get access

Abstract

Background

Different types of reactive oxygen metabolites (ROMs) are known to be involved in carcinogenesis. Several studies have emphasized the formation of ROMs in ischemic tissues and in cases of inflammation. The increased amounts of ROMs in tumor tissues can either be because of their causative effects or because they are produced by the tumor itself. Our study aimed to investigate and compare the levels of ROMs in tumor tissue and adjacent lung parenchyma obtained from patients with lung cancer.

Methods

Fifteen patients (all male, mean age 63.6 ± 9 years) with non-small cell lung cancer were enrolled in the study. All patients were smokers. Of the patients with lung cancer, twelve had epidermoid carcinoma and three had adenocarcinoma. During anatomical resection of the lung, tumor tissue and macroscopically adjacent healthy lung parenchyma (control) that was 5 cm away from the tumor were obtained. The tissues were freshly frozen and stored at −20°C. The generation of ROMs was monitored using luminol- and lucigenin-enhanced chemiluminescence (CL) techniques.

Results

Both luminol (specific for .OH, H2O2, and HOCl-) and lucigenin (selective for O2.-) CL measurements were significantly higher in tumor tissues than in control tissues (P <0.001). Luminol and lucigenin CL measurements were 1.93 ± 0.71 and 2.5 ± 0.84 times brighter, respectively, in tumor tissues than in the adjacent parenchyma (P = 0.07).

Conclusion

In patients with lung cancer, all ROM levels were increased in tumor tissues when compared with the adjacent lung tissue. Because the increase in lucigenin concentration, which is due to tissue ischemia, is higher than the increase in luminol, which is directly related to the presence and severity of inflammation, ischemia may be more important than inflammation for tumor development in patients with lung cancer.
Appendix
Available only for authorised users
Literature
1.
go back to reference Masri F: Role of nitric oxide and its metabolites as metabolites as potential markers in lung cancer. Ann Thorac Med. 2010, 5: 123-127. 10.4103/1817-1737.65036.PubMedCentralCrossRefPubMed Masri F: Role of nitric oxide and its metabolites as metabolites as potential markers in lung cancer. Ann Thorac Med. 2010, 5: 123-127. 10.4103/1817-1737.65036.PubMedCentralCrossRefPubMed
2.
go back to reference Bilello KS, Murin S, Matthay RA: Epidemology, etiology and prevention of lung cancer. Clin Chest Med. 2002, 23: 1-15. 10.1016/S0272-5231(03)00057-1.CrossRefPubMed Bilello KS, Murin S, Matthay RA: Epidemology, etiology and prevention of lung cancer. Clin Chest Med. 2002, 23: 1-15. 10.1016/S0272-5231(03)00057-1.CrossRefPubMed
3.
go back to reference Chow CK: Cigarette smoking and oxidative damage in the lung. Ann NY Acad Sci. 1993, 28: 289-298.CrossRef Chow CK: Cigarette smoking and oxidative damage in the lung. Ann NY Acad Sci. 1993, 28: 289-298.CrossRef
4.
go back to reference Zieba M, Suwalski M, Kwiatkowska S, Piasecka G, Grzelewska-Rzymowska I, Stolarek R, Nowak D: Comparison of hydrogen peroxide generation and the content of lipid peroxidation products in lung cancer tissue and pulmonary parenchyma. Resp Med. 2000, 94: 800-805. 10.1053/rmed.2000.0825.CrossRef Zieba M, Suwalski M, Kwiatkowska S, Piasecka G, Grzelewska-Rzymowska I, Stolarek R, Nowak D: Comparison of hydrogen peroxide generation and the content of lipid peroxidation products in lung cancer tissue and pulmonary parenchyma. Resp Med. 2000, 94: 800-805. 10.1053/rmed.2000.0825.CrossRef
5.
go back to reference Yoo DG, Song YJ, Cho EJ, Lee SK, Park JB, Yu JH, Lim SP, Kim JM, Jeon BH: Alteration of APE1/ref-1 expression in non-small cell lung cancer: The implications of impaired extracellular superoxide dismutase and catalase antioxidant systems. Lung Cancer. 2008, 60: 277-284. 10.1016/j.lungcan.2007.10.015.CrossRefPubMed Yoo DG, Song YJ, Cho EJ, Lee SK, Park JB, Yu JH, Lim SP, Kim JM, Jeon BH: Alteration of APE1/ref-1 expression in non-small cell lung cancer: The implications of impaired extracellular superoxide dismutase and catalase antioxidant systems. Lung Cancer. 2008, 60: 277-284. 10.1016/j.lungcan.2007.10.015.CrossRefPubMed
6.
go back to reference Wiseman H, Halliwell B: Damage to DNA by reactive oxygen and nitrogen species: Role in inflammatory disease and progression to cancer. Biochem J. 1996, 313: 17-19.PubMedCentralCrossRefPubMed Wiseman H, Halliwell B: Damage to DNA by reactive oxygen and nitrogen species: Role in inflammatory disease and progression to cancer. Biochem J. 1996, 313: 17-19.PubMedCentralCrossRefPubMed
7.
go back to reference Esme H, Cemek M, Sezer M, Saglam H, Demir A, Melek H, Unlu M: High levels of oxidative stress in patients with advanced lung cancer. Respirology. 2008, 13: 112-116. 10.1111/j.1440-1843.2007.01212.x.CrossRefPubMed Esme H, Cemek M, Sezer M, Saglam H, Demir A, Melek H, Unlu M: High levels of oxidative stress in patients with advanced lung cancer. Respirology. 2008, 13: 112-116. 10.1111/j.1440-1843.2007.01212.x.CrossRefPubMed
8.
go back to reference Chung FL, Chen HJ, Guttenplan JB, Nishikawa A, Hard GC: 2,3-epoxy-4-hydroxynonanal as a potential tumor-indicating agent of lipid peroxidation. Carcinogenesis. 1993, 14: 2073-2077. 10.1093/carcin/14.10.2073.CrossRefPubMed Chung FL, Chen HJ, Guttenplan JB, Nishikawa A, Hard GC: 2,3-epoxy-4-hydroxynonanal as a potential tumor-indicating agent of lipid peroxidation. Carcinogenesis. 1993, 14: 2073-2077. 10.1093/carcin/14.10.2073.CrossRefPubMed
9.
go back to reference Haklar G, Ozveri ES, Yuksel M, Aktan AO, Yalcin AS: Different kinds of reactive oxygen and nitrogen species were detected in colon and breast tumors. Cancer Lett. 2001, 165: 219-224. 10.1016/S0304-3835(01)00421-9.CrossRefPubMed Haklar G, Ozveri ES, Yuksel M, Aktan AO, Yalcin AS: Different kinds of reactive oxygen and nitrogen species were detected in colon and breast tumors. Cancer Lett. 2001, 165: 219-224. 10.1016/S0304-3835(01)00421-9.CrossRefPubMed
10.
go back to reference Kricka LJ: Clinical applications of chemiluminescence. Anal Chim Acta. 2003, 500: 279-286. 10.1016/S0003-2670(03)00809-2.CrossRef Kricka LJ: Clinical applications of chemiluminescence. Anal Chim Acta. 2003, 500: 279-286. 10.1016/S0003-2670(03)00809-2.CrossRef
11.
go back to reference Mooney LA, Perera FP, Van Bennekum AM, Blaner WS, Karkoszka J, Covey L, Hsu Y, Cooper TB, Frenkel K: Gender differences in autoantibodies to oxidative DNA base damage in cigarette smokers. Cancer Epidem Biomar. 2001, 10: 641-648. Mooney LA, Perera FP, Van Bennekum AM, Blaner WS, Karkoszka J, Covey L, Hsu Y, Cooper TB, Frenkel K: Gender differences in autoantibodies to oxidative DNA base damage in cigarette smokers. Cancer Epidem Biomar. 2001, 10: 641-648.
12.
go back to reference Feig DI, Reid TM, Loeb LA: Reactive oxygen species in tumorigenesis. Cancer Res. 1994, 54: 1890-1894. Feig DI, Reid TM, Loeb LA: Reactive oxygen species in tumorigenesis. Cancer Res. 1994, 54: 1890-1894.
13.
go back to reference Gencer M, Ceylan E, Aksoy N, Uzun K: Association of serum reactive oxygen metabolite levels with different histopathological types of lung cancer. Respiration. 2006, 73: 520-524. 10.1159/000088895.CrossRefPubMed Gencer M, Ceylan E, Aksoy N, Uzun K: Association of serum reactive oxygen metabolite levels with different histopathological types of lung cancer. Respiration. 2006, 73: 520-524. 10.1159/000088895.CrossRefPubMed
14.
go back to reference Üneri C, Sari M, Bağlam T, Polat Ş, Yüksel M: Effects of vitamin E on cigarette smoke induced oxidative damage in larynx and lung. Laryngoscope. 2006, 116: 97-100. 10.1097/01.mlg.0000186504.53216.d1.CrossRefPubMed Üneri C, Sari M, Bağlam T, Polat Ş, Yüksel M: Effects of vitamin E on cigarette smoke induced oxidative damage in larynx and lung. Laryngoscope. 2006, 116: 97-100. 10.1097/01.mlg.0000186504.53216.d1.CrossRefPubMed
15.
go back to reference Ilonen IK, Rasanen JV, Sihvo EL, Knuuttila A, Salmenkivi KM, Ahotupa MO, Kinnula VL, Salo JA: Oxidative stress in non-small cell lung cancer: role of nicotinamide adenine dinucleotide phosphate oxidase and glutathione. Acta Oncol. 2009, 48: 1054-1061. 10.1080/02841860902824909.CrossRefPubMed Ilonen IK, Rasanen JV, Sihvo EL, Knuuttila A, Salmenkivi KM, Ahotupa MO, Kinnula VL, Salo JA: Oxidative stress in non-small cell lung cancer: role of nicotinamide adenine dinucleotide phosphate oxidase and glutathione. Acta Oncol. 2009, 48: 1054-1061. 10.1080/02841860902824909.CrossRefPubMed
16.
go back to reference van der Brekel AJS, Schols AMW, Dentener MA, ten Velde GP, Buurman WA, Wouters EF: Metabolism in patients with small cell lung carcinoma compared with patients with non-small cell lung carcinoma and healthy controls. Thorax. 1997, 52: 338-341. 10.1136/thx.52.4.338.CrossRef van der Brekel AJS, Schols AMW, Dentener MA, ten Velde GP, Buurman WA, Wouters EF: Metabolism in patients with small cell lung carcinoma compared with patients with non-small cell lung carcinoma and healthy controls. Thorax. 1997, 52: 338-341. 10.1136/thx.52.4.338.CrossRef
17.
go back to reference Leroyer V, Werner L, Shaughnessy S, Goddard GJ, Orr FW: Chemiluminescence and oxygen radical generation by Walker carcinoma cells following chemotactic stimulation. Cancer Res. 1987, 47: 4771-4775.PubMed Leroyer V, Werner L, Shaughnessy S, Goddard GJ, Orr FW: Chemiluminescence and oxygen radical generation by Walker carcinoma cells following chemotactic stimulation. Cancer Res. 1987, 47: 4771-4775.PubMed
18.
go back to reference Sorg O: Oxidative stress: a theoretical model or a biological reality?. C R Biol. 2004, 327: 649-662. 10.1016/j.crvi.2004.05.007.CrossRefPubMed Sorg O: Oxidative stress: a theoretical model or a biological reality?. C R Biol. 2004, 327: 649-662. 10.1016/j.crvi.2004.05.007.CrossRefPubMed
19.
go back to reference Piyathilake CJ, Bell WC, Oelschlager DK, Heimburger DC, Grizzle WE: The pattern of expression of Mn and Cu-Zn superoxide dismutase varies among squamous cell cancers of the lung, larynx, and oral cavity. Head Neck. 2002, 24: 859-867. 10.1002/hed.10135.CrossRefPubMed Piyathilake CJ, Bell WC, Oelschlager DK, Heimburger DC, Grizzle WE: The pattern of expression of Mn and Cu-Zn superoxide dismutase varies among squamous cell cancers of the lung, larynx, and oral cavity. Head Neck. 2002, 24: 859-867. 10.1002/hed.10135.CrossRefPubMed
20.
go back to reference Ohoi I, Sone K, Tobari H, Kawano E, Nakamura K: A simple chemiluminescence method for measuring oxygen-derived free radicals generated in oxygenated rat myocardium. Jpn J Pharmacol. 1993, 61: 101-107. 10.1254/jjp.61.101.CrossRefPubMed Ohoi I, Sone K, Tobari H, Kawano E, Nakamura K: A simple chemiluminescence method for measuring oxygen-derived free radicals generated in oxygenated rat myocardium. Jpn J Pharmacol. 1993, 61: 101-107. 10.1254/jjp.61.101.CrossRefPubMed
21.
go back to reference Ohoi I, Tobari H, Nakamura K: Measurement of oxygen-derived free radical generation in the regionally-ischemic rat heart by the chemiluminescence method. Jpn J Pharmacol. 1993, 62: 415-418. 10.1254/jjp.62.415.CrossRefPubMed Ohoi I, Tobari H, Nakamura K: Measurement of oxygen-derived free radical generation in the regionally-ischemic rat heart by the chemiluminescence method. Jpn J Pharmacol. 1993, 62: 415-418. 10.1254/jjp.62.415.CrossRefPubMed
22.
go back to reference Cicenas J, Küng W, Eppenberger U, Eppenberger-Castori S: Increased level of phosphorylated ShcA measured by chemiluminescence-linked immunoassay is a predictor of good prognosis in primary breast cancer expressing low levels of estrogen receptor. Cancers. 2010, 2: 153-164. 10.3390/cancers2010153.PubMedCentralCrossRefPubMed Cicenas J, Küng W, Eppenberger U, Eppenberger-Castori S: Increased level of phosphorylated ShcA measured by chemiluminescence-linked immunoassay is a predictor of good prognosis in primary breast cancer expressing low levels of estrogen receptor. Cancers. 2010, 2: 153-164. 10.3390/cancers2010153.PubMedCentralCrossRefPubMed
23.
go back to reference Toklu H, Şehirli Ö, Şahin H, Çetinel Ş, Yeğen BC, Şener G: Resveratrol supplementation protects against chronic nicotine-induced oxidative damage and organ dysfunction in the rat urogenital system. Marmara Pharmaceutical Journal. 2010, 14: 29-40.CrossRef Toklu H, Şehirli Ö, Şahin H, Çetinel Ş, Yeğen BC, Şener G: Resveratrol supplementation protects against chronic nicotine-induced oxidative damage and organ dysfunction in the rat urogenital system. Marmara Pharmaceutical Journal. 2010, 14: 29-40.CrossRef
Metadata
Title
Detection of reactive oxygen metabolites in malignant and adjacent normal tissues of patients with lung cancer
Authors
Hacer Kuzu Okur
Meral Yuksel
Tunc Lacin
Volkan Baysungur
Erdal Okur
Publication date
01-12-2013
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2013
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/1477-7819-11-9

Other articles of this Issue 1/2013

World Journal of Surgical Oncology 1/2013 Go to the issue