8-nitroguanine and Neoplasms

Inflammation can be induced by chronic infection, inflammatory diseases and physicochemical factors. Chronic inflammation is estimated to contribute to approximately 25% of human cancers. Under inflammatory conditions, inflammatory and epithelial cells release reactive oxygen (ROS) and nitrogen species (RNS), which are capable of causing DNA damage, including the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-nitroguanine. We reported that 8-nitroguanine was clearly formed at the sites of cancer induced by infectious agents including

Topics: 8-Hydroxy-2'-Deoxyguanosine; Carcinogenesis; Deoxyguanosine; DNA Damage; Guanine; Humans; Inflammation; Mutation; Neoplasms; Nitric Oxide Synthase Type II; Reactive Nitrogen Species; Reactive Oxygen Species; Tumor Hypoxia

Topics: Animals; Bacteria; Guanine; Humans; Immunity, Innate; Inflammation; Mutation; Neoplasms; Nitric Oxide; Reactive Nitrogen Species; Signal Transduction; Viruses

Infection and chronic inflammation are proposed to contribute to carcinogenesis through inflammation-related mechanisms. Infection with hepatitis C virus, Helicobacter pylori and the liver fluke, Opisthorchis viverrini (OV), are important risk factors for hepatocellular carcinoma (HCC), gastric cancer and cholangiocarcinoma, respectively. Inflammatory bowel diseases (IBDs) and oral diseases, such as oral lichen planus (OLP) and leukoplakia, are associated with colon carcinogenesis and oral squamous cell carcinoma (OSCC), respectively. We performed a double immunofluorescence labeling study and found that nitrative and oxidative DNA lesion products, 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), were formed and inducible nitric oxide synthase (iNOS) was expressed in epithelial cells and inflammatory cells at the site of carcinogenesis in humans and animal models. Antibacterial, antiviral and antiparasitic drugs dramatically diminished the formation of these DNA lesion markers and iNOS expression. These results suggest that oxidative and nitrative DNA damage occurs at the sites of carcinogenesis, regardless of etiology. Therefore, it is considered that excessive amounts of reactive nitrogen species produced via iNOS during chronic inflammation may play a key role in carcinogenesis by causing DNA damage. On the basis of our results, we propose that 8-nitroguanine is a promising biomarker to evaluate the potential risk of inflammation-mediated carcinogenesis.

Topics: Animals; Cholangiocarcinoma; Colonic Neoplasms; DNA Damage; Guanine; Humans; Infections; Inflammation; Inflammatory Bowel Diseases; Liver Neoplasms; Mice; Mouth Neoplasms; Neoplasms; Oxidative Stress

Topics: Asthma; Biomarkers; Carbon Monoxide; Chromatography, Gas; Chromatography, High Pressure Liquid; Clinical Enzyme Tests; Enzyme-Linked Immunosorbent Assay; Guanine; Infections; Neoplasms; Nitric Oxide; Pulmonary Disease, Chronic Obstructive; Reference Values; Sepsis; Tyrosine

Three stochastic microsensors based on graphite powder modified with three different oleamides: N-(2-piperidin-1-ylethyl)oleamide, N-(3,4-dihydroxyphenethyl)oleamide and N-(2-morpholinoethyl)oleamide, were designed, characterized, and used to assess DNA damage in cancer by assaying two biomarkers namely 8-nitroguanine and 8-hydroxy-2'-deoxyguanosine. The two biomarkers were determined from urine and whole blood samples. The characterization of the microsensors was done at two pHs 7.40 and 3.00. The best microsensor for the simultaneous determination of biomarkers in whole blood and urine samples was the one based on the graphite paste modified with N-(3,4-dihydroxyphenethyl)oleamide. The results indicated that the proposed microsensors can be reliably used for pattern recognition and quantitative determination of 8-nitroguanine and 8-hydroxy-2'-deoxyguanosine in whole blood and urine, and accordingly, for the assessment of DNA damage in cancer patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers, Tumor; Biosensing Techniques; DNA Damage; Graphite; Guanine; Humans; Neoplasms

A sensitive and low-cost analytical method has been developed to determine 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-nitroguanine (8-NO(2)Gua) based on capillary electrophoresis with amperometric detection (CE-AD) after solid phase extraction (SPE). Under optimized condition, these two markers were well separated from other components coexisting in urine, exhibiting a linear calibration over the concentration range of 0.1-50.0 μg/mL with the detection limits ranging from 0.02 to 0.06 μg/mL. The relative standard deviations (RSDs) were in the range of 0.1-2.1% for peak area, 0.1-1.5% for migration time, respectively. The average recovery and RSD were within the range of 100.0-108.0% and 0.1-1.7%, respectively. It was found that the urinary contents of 8-OHdG and 8-NO(2)Gua in cancer patients were significantly higher than those in healthy ones.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; Deoxyguanosine; DNA Damage; Electrophoresis, Capillary; Female; Guanine; Humans; Hydrogen-Ion Concentration; Limit of Detection; Male; Middle Aged; Neoplasms; Reproducibility of Results; Solid Phase Extraction

Chronic inflammation is induced by various infectious/infected agents and by many physical, chemical and immunological factors. Many malignancies arise from areas of infection and inflammation. Reactive oxygen species and reactive nitrogen species are considered to play the key role in inflammation-associated carcinogenesis by causing oxidative and nitrative DNA damage. 8-Nitroguanine is a mutagenic nitrative DNA lesion formed during inflammation. Development of a detection method for 8-nitroguanine would provide an insight into the mechanism of inflammation-associated carcinogenesis and the assessment of carcinogenic risk in patients with inflammatory diseases. We established the method to produce highly sensitive and specific anti-8-nitroguanine rabbit polyclonal antibody, and detect 8-nitroguanine formation in biopsy specimens and animal tissues by immunohistochemistry. We have found that 8-nitroguanine is formed at the sites of carcinogenesis regardless of etiology, and proposed the possibility that 8-nitroguanine is a potential biomarker to evaluate the risk of inflammation-associated carcinogenesis. In this paper, we describe the procedures of these experiments and the application to clinical specimens and animal tissues.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Biomarkers, Tumor; Deoxyguanosine; DNA Damage; Fluorescent Antibody Technique, Indirect; Guanine; Humans; Inflammation; Neoplasms; Rabbits; Reactive Nitrogen Species