Activated neutrophils inhibit nucleotide excision repair in human pulmonary epithelial cells: role of myeloperoxidase

Güngör, Nejla; Godschalk, Roger; Pachen, D. M. F. A.; Schooten, Frederik J. van; Knaapen, Ad M.

doi:10.1096/fj.07-8163com

Cited by 65 publications

(24 citation statements)

References 48 publications

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“…MPO is involved in the bioactivation of inhaled polycyclic aromatic hydrocarbons to generate DNA binding metabolites that are mutagenic [43, 44]. HOCl inhibits repair of DNA strand breaks and nucleotide excision [45–47]. The detection of higher levels of MPO in cancer tissue is consistent with a role in carcinogenesis.…”

Section: Discussionmentioning

confidence: 98%

Association of myeloperoxidase with ovarian cancer

et al. 2013

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Myeloperoxidase (MPO) is an oxidant generating enzyme normally restricted to myeloid cells, however aberrant MPO expression has been found to occur in non-myeloid cells in some disease states. The functional -463GA promoter polymorphism alters MPO expression levels. The -463G is within an SP1 binding site and is associated with higher gene expression. The G allele is most frequent with ~62% of European populations being GG homozygotes. The GA polymorphism has been associated with risk or survival in a variety of cancers including lung and breast cancer. In this study we determined the frequency of the -463G/A polymorphism in 230 ovarian cancer patients, 75 patients with borderline ovarian tumors, and 299 healthy controls. The GG genotype was found to be overrepresented in patients with early stage ovarian cancer (83.3% GG, p = 0.008) as compared to healthy controls (62% GG), suggesting MPO oxidants may increase risk. Immunohistochemical analysis revealed MPO expression in a subset of columnar ovarian epithelial carcinoma cells in early stage carcinomas.

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Section: Discussionmentioning

confidence: 98%

Association of myeloperoxidase with ovarian cancer

et al. 2013

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“…The generation of oxidants by neutrophils is critical to host defenses against microbial pathogens [50,51] . Oxidant production begins with a cytoplasmic membraneassociated NADPH oxidase, which reduces molecular oxygen to superoxide.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Infiltration and Oxidative Stress May Play a Critical Role in Methotrexate-Induced Renal Damage

Kolli¹,

Abraham²,

Isaac

et al. 2009

Chemotherapy

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Background: Nephrotoxicity is one of the adverse side effects of methotrexate (MTX) chemotherapy. The mechanism of renotoxicity of MTX is not fully understood. It is essential to understand the mechanism of nephrotoxicity of MTX in order to diminish the side effects and hence maximize the benefits of chemotherapy. Objectives: The aim of the study was to verify whether oxidative stress and neutrophil infiltration play a role in MTX-induced renal damage using a rat model. Methods: Adult male rats were administered MTX at the dose of 7 mg/kg body weight intraperitoneally for 3 consecutive days and sacrificed 12 or 24 h after the last dose. Vehicle-treated rats served as controls. The kidneys were removed and used for light microscopic and biochemical studies. Myeloperoxidase activity, a marker of neutrophil infiltration was measured in kidney homogenates along with the markers of oxidative damage including protein carbonyl content, protein thiol and malondialdehyde. The activities of the antioxidant enzymes, namely glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase, were also assayed. Results: MTX treatment induced damage to the glomeruli and tubules. Plasma creatinine levels in the MTX-treated rats were significantly elevated compared with controls. A significant increase in myeloperoxidase activity (p < 0.05) was observed in the kidneys of MTX-treated rats. Protein carbonyl content and malondialdehyde, sensitive and reliable markers of oxidative damage to proteins and lipids, respectively, were significantly elevated (p < 0.01) in the kidneys of MTX-treated rats compared with controls. The activities of the antioxidant enzymes, namely, superoxide dismutase and glutathione peroxidase, were significantly elevated (p < 0.01 and p < 0.05, respectively) in kidneys of rats following MTX treatment. Conclusion: The results of the present study provide evidence for the role of neutrophil infiltration and oxidative stress in MTX-induced renal damage. Administration of inhibitors of myeloperoxidase or scavenging hypochlorous acid, the product of myeloperoxidase, by supplementation with antioxidants as an adjuvant therapy may be promising in alleviating the renal side effect of MTX.

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“…Furthermore, it has been established that the type of DNA base modifications, as detected in target cells exposed to H 2 O 2 , is similar to the damage induced by activated neutrophils. Also, hypochlorous acid has been shown to be an inhibitor of DNA strand break repair (28). Hypochlorous acid is a relatively stable and membrane-diffusible molecule that can reach the nucleus.…”

Section: Inflammation As Indicator Of Colorectal Cancer Riskmentioning

confidence: 99%

Myeloperoxidase-Positive Cell Infiltration in Colorectal Carcinogenesis as Indicator of Colorectal Cancer Risk

Roncucci¹,

Mora²,

Mariani³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Colorectal mucosa is targeted by toxic agents, which can initiate or promote colon cancer. The mechanism of damage might be a focal irritation with loss of normal epithelial cell barrier function. Genetic alterations in tumors may also affect host inflammatory response. The aim of this study was to define the extent of inflammation in colorectal mucosa, along colorectal carcinogenesis, and in microsatellite stable and unstable colorectal carcinomas. We collected 103 samples of normal colorectal mucosa from 65 patients (35 with colorectal cancer or adenoma, 8 with inflammatory bowel diseases, and 22 controls with normal colonoscopy). We also examined 24 aberrant crypt foci, 14 hyperplastic polyps, 16 adenomas, and 67 samples of colorectal carcinoma. Immunohistochemistry was used to count myeloperoxidase (MPO)-positive cells (neutrophils and monocytes) in Â100

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Activated neutrophils inhibit nucleotide excision repair in human pulmonary epithelial cells: role of myeloperoxidase

Cited by 65 publications

References 48 publications

Association of myeloperoxidase with ovarian cancer

Association of myeloperoxidase with ovarian cancer

Neutrophil Infiltration and Oxidative Stress May Play a Critical Role in Methotrexate-Induced Renal Damage

Myeloperoxidase-Positive Cell Infiltration in Colorectal Carcinogenesis as Indicator of Colorectal Cancer Risk

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