Molecular mechanisms of oxidative stress‐induced carcinogenesis: From epidemiology to oxygenomics

Toyokuni, Shinya

doi:10.1002/iub.61

Cited by 144 publications

(87 citation statements)

References 90 publications

(66 reference statements)

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“…(15,25) In the present paper, we not only re-evaluated the catalytic activities of UICC asbestos fibers for the generation of free radicals but also identified several novel characteristics of these fibers in asbestos-induced oxidative DNA damage.…”

Section: Discussionmentioning

confidence: 99%

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Characteristics and modifying factors of asbestos‐induced oxidative DNA damage

et al. 2008

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Respiratory exposure to asbestos has been linked with mesothelioma in humans. However, its carcinogenic mechanism is still unclear. Here we studied the ability of chrysotile, crocidolite and amosite fibers to induce oxidative DNA damage and the modifying factors using four distinct approaches. Electron spin resonance analyses revealed that crocidolite and amosite containing high amounts of iron, but not chrysotile, catalyzed hydroxyl radical generation in the presence of H 2 O 2 , which was enhanced by an iron chelator, nitrilotriacetic acid, and suppressed by desferal. Natural iron chelators, such as citrate, adenosine 5′-triphosphate and guanosine 5′-triphosphate, did not inhibit this reaction. Second, we used time-lapse video microscopy to evaluate how cells cope with asbestos fibers. RAW264.7 cells, MeT-5 A and HeLa cells engulfed asbestos fibers, which reached not only cytoplasm but also the nucleus. Third, we utilized supercoiled plasmid DNA to evaluate the ability of each asbestos to induce DNA double strand breaks (DSB). Crocidolite and amosite, but not chrysotile, induced DNA DSB in the presence of iron chelators. We cloned the fragments to identify break sites. DSB occurred preferentially within repeat sequences and between two G:C sequences. Finally, i.p. administration of each asbestos to rats induced not only formation of nuclear 8-hydroxy-2′-deoxyguanosine in the mesothelia, spleen, liver and kidney but also significant iron deposits in the spleen. Together with the established carcinogenicity of i.p. chrysotile, our data suggest that asbestos-associated catalytic iron, whether constitutional or induced by other mechanisms, plays an important role in asbestos-induced carcinogenesis and that chemoprevention may be possible through targeting the catalytic iron. (Cancer Sci 2008; 99: 2142-2151) A sbestos fibers have been heavily used in industry from World War II to the present because of their durability, heat-resistance and low cost.(1,2) However, in 1987, the International Agency for Research on Cancer (IARC) designated asbestos fibers as a group I (definite) carcinogen for humans (http:// monographs.iarc.fr/ENG/Classification/crthgr01.php), and asbestos fibers were banned in many European and North American countries in the 1990s.(1,2) In June of 2005, asbestos-associated deaths suddenly attracted social attention in Japan because it was reported that 79 people who worked in factories using asbestos had been killed by an asbestos-associated rare cancer called diffuse malignant mesothelioma (DMM) over the past 26 years. Furthermore, people who lived near those factories also suffered from the same fatal disease.(4) The characteristics of DMM are as follows: (i) it is associated with repeated asbestos exposure; (5,6) (ii) once diagnosed, prognosis is poor; (7) and (iii) it takes 30-40 years after the start of asbestos exposure for DMM to occur.(5,6) It is expected that the incidence of DMM in Japan will peak in 2025 with 100 000 predicted deaths from this neoplasm. (8) There are several hypotheses a...

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Section: Discussionmentioning

confidence: 99%

“…Indeed, excess iron is carcinogenic not only to animals, but also to humans. (14,15) In the present paper, we describe novel characteristics and modifying factors for asbestos-associated oxidative DNA damage. …”

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Characteristics and modifying factors of asbestos‐induced oxidative DNA damage

et al. 2008

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“…R edox imbalance between reactive species and endogenous antioxidants, which results in oxidative damage to biologic molecules and impairment in signaling pathways [(i.e., in oxidative stress (145)], has been widely implicated in many ailments, including central nervous system pathologies (46,51,61,122,219,330) [e.g., amyotrophic lateral sclerosis, (46), Parkinson's disease (219), bipolar disorder (330), Alzheimer's disease (61)], cardiovascular conditions (61,112), pulmonary conditions (65,153), diabetes (111,154), eye diseases (19,235), aging (290,323,236), cancer (52,70,317), radiation injury (220), pain=chronic morphine tolerance (89), Fanconi anemia (229). Reactive species, such as nitric oxide ( · NO), superoxide (O 2 ·À ), hydrogen peroxide (H 2 O 2 ), peroxynitrite (ONOO -), and others have been widely recognized as signaling species that, by affecting redox-based cellular transcriptional activity, control inflammatory and immune responses and enhance secondary oxidative stress (27,47,96,151,188,273,276,298,335,336).…”

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confidence: 99%

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Batinić‐Haberle

Rebouças

Spasojević

2010

Antioxidants & Redox Signaling

467

689

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Oxidative stress has become widely viewed as an underlying condition in a number of diseases, such as ischemia-reperfusion disorders, central nervous system disorders, cardiovascular conditions, cancer, and diabetes. Thus, natural and synthetic antioxidants have been actively sought. Superoxide dismutase is a first line of defense against oxidative stress under physiological and pathological conditions. Therefore, the development of therapeutics aimed at mimicking superoxide dismutase was a natural maneuver. Metalloporphyrins, as well as Mn cyclic polyamines, Mn salen derivatives and nitroxides were all originally developed as SOD mimics. The same thermodynamic and electrostatic properties that make them potent SOD mimics may allow them to reduce other reactive species such as peroxynitrite, peroxynitrite-derived CO 3 _ À , peroxyl radical, and less efficiently H 2 O 2 . By doing so SOD mimics can decrease both primary and secondary oxidative events, the latter arising from the inhibition of cellular transcriptional activity. To better judge the therapeutic potential and the advantage of one over the other type of compound, comparative studies of different classes of drugs in the same cellular and=or animal models are needed. We here provide a comprehensive overview of the chemical properties and some in vivo effects observed with various classes of compounds with a special emphasis on porphyrin-based compounds. Antioxid. Redox Signal. 13, 877-918.

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“…The exact interplay between this system biology and its functional genomics, integrating proteomic and genetic with end-product metabolic information as an early cancer screening tool, is at present not completely known. In recent years several studies have assessed the capacity of breath analysis to diagnose lung cancer 7 , asbestos exposure 11 , breast cancer 9 , malignant melanoma 10 , aerodigestive squamous cell carcinoma 25 and hepatocellular carcinoma 12 .…”

Section: Discussionmentioning

confidence: 99%

“…Alteration in VOC production in patients with cancer has been postulated to relate to (per)oxygenation of cell membrane-based polyunsaturated fatty acids resulting from genetic and/or protein mutations within tumour cells and the increased relative prevalence of reactive oxygen species within cancer cells 6,7 . Those VOCs, wherever produced in the body, can reach the pulmonary alveoli where they are exhaled, permitting an objective method of measurement.…”

Section: Introductionmentioning

confidence: 99%

Exhaled volatile organic compounds identify patients with colorectal cancer (Br J Surg 2013; 100: 144–150)

Zbar

2013

Journal of British Surgery

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Background: An effective screening tool for colorectal cancer is still lacking. Analysis of the volatile organic compounds (VOCs) linked to cancer is a new frontier in cancer screening, as tumour growth involves several metabolic changes leading to the production of specific compounds that can be detected in exhaled breath. This study investigated whether patients with colorectal cancer have a specific VOC pattern compared with the healthy population.Methods: Exhaled breath was collected in an inert bag (Tedlar  ) from patients with colorectal cancer and healthy controls (negative at colonoscopy), and processed offline by thermal-desorber gas chromatography-mass spectrometry to evaluate the VOC profile. During the trial phase VOCs of interest were identified and selected, and VOC patterns able to discriminate patients from controls were set up; in the validation phase their discriminant performance was tested on blinded samples. A probabilistic neural network (PNN) validated by the leave-one-out method was used to identify the pattern of VOCs that better discriminated between the two groups.

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Molecular mechanisms of oxidative stress‐induced carcinogenesis: From epidemiology to oxygenomics

Cited by 144 publications

References 90 publications

Characteristics and modifying factors of asbestos‐induced oxidative DNA damage

Characteristics and modifying factors of asbestos‐induced oxidative DNA damage

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Exhaled volatile organic compounds identify patients with colorectal cancer (Br J Surg 2013; 100: 144–150)

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