Role of Nitrative DNA Damage in Inflammation‐Related Carcinogenesis

Hiraku, Yusuke; Kawanishi, Shosuke

doi:10.1002/9781118826621.ch4

Cited by 8 publications

(12 citation statements)

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“…Inflammation is the primary source of RNS, and the formation of nitrative DNA lesions, including 8-nitroG, may contribute to MWCNT-induced carcinogenesis. We previously demonstrated that 8-nitroG was formed at the sites of inflammation-related carcinogenesis in animal models and clinical specimens [ 19 – 22 ]. The glycosidic bond between 8-nitroG and deoxyribose is chemically unstable and thus 8-nitroG can be spontaneously released to form an apurinic site [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…8-Nitroguanine (8-nitroG) is a mutagenic DNA lesion produced by the reaction of guanine with peroxynitrite (ONOO - ), which is formed from nitric oxide (NO) and superoxide (O 2 - ) generated under inflammatory conditions [ 18 ]. We have demonstrated that 8-nitroG is formed at the sites of carcinogenesis in various animal models and clinical specimens of cancer-prone inflammatory diseases [ 19 – 22 ], including asbestos exposure [ 23 , 24 ]. We have reported that multi-walled CNT (MWCNT) induced 8-nitroG formation in a lung epithelial cell line and this process involves endocytosis [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Multi-walled carbon nanotube induces nitrative DNA damage in human lung epithelial cells via HMGB1-RAGE interaction and Toll-like receptor 9 activation

Hiraku

Guo

et al. 2015

Part Fibre Toxicol

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BackgroundCarbon nanotube (CNT) is used for various industrial purposes, but exhibits carcinogenic effects in experimental animals. Chronic inflammation in the respiratory system may participate in CNT-induced carcinogenesis. 8-Nitroguanine (8-nitroG) is a mutagenic DNA lesion formed during inflammation. We have previously reported that multi-walled CNT (MWCNT) induced 8-nitroG formation in lung epithelial cells and this process involved endocytosis. To clarify the mechanism of CNT-induced carcinogenesis, we examined the role of Toll-like receptor (TLR) 9, which resides in endosomes and lysosomes, in 8-nitroG formation in human lung epithelial cell lines.MethodsWe performed immunocytochemistry to examine 8-nitroG formation in A549 and HBEpC cells treated with MWCNT with a length of 1-2 μm (CNT-S) or 5-15 μm (CNT-L) and a diameter of 20-40 nm. We examined inhibitory effects of endocytosis inhibitors, small interfering RNA (siRNA) for TLR9, and antibodies against high-mobility group box-1 (HMGB1) and receptor for advanced glycation end-products (RAGE) on 8-nitroG formation. The release of HMGB1 and double-stranded DNA (dsDNA) into the culture supernatant from MWCNT-treated cells was examined by ELISA and fluorometric analysis, respectively. The association of these molecules was examined by double immunofluorescent staining and co-immunoprecipitation.ResultsCNT-L significantly increased 8-nitroG formation at 0.05 μg/ml in A549 cells and its intensity reached a maximum at 1 μg/ml. CNT-L tended to induce stronger cytotoxicity and 8-nitroG formation than CNT-S. Endocytosis inhibitors, TLR9 siRNA and antibodies against HMGB1 and RAGE largely reduced MWCNT-induced 8-nitroG formation. MWCNT increased the release of HMGB1 and dsDNA from A549 cells into culture supernatant. The culture supernatant of MWCNT-exposed cells induced 8-nitroG formation in fresh A549 cells. Double immunofluorescent staining and co-immunoprecipitation showed that TLR9 was associated with HMGB1 and RAGE in lysosomes of MWCNT-treated cells.ConclusionsMWCNT induces injury or necrosis of lung epithelial cells, which release HMGB1 and DNA into the extracellular space. The HMGB1-DNA complex binds to RAGE on neighboring cells and then CpG DNA is recognized by TLR9 in lysosomes, leading to generation of nitric oxide and 8-nitroG formation. This is the first study demonstrating that TLR9 and related molecules participate in MWCNT-induced genotoxicity and may contribute to carcinogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-016-0127-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multi-walled carbon nanotube induces nitrative DNA damage in human lung epithelial cells via HMGB1-RAGE interaction and Toll-like receptor 9 activation

Hiraku

Guo

et al. 2015

Part Fibre Toxicol

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“…In addition, DNA can also be modified directly by ROS and RNS to 8-nitro-dG and 8-Oxo-dG [28] . All of these DNA changes have been detected in human specimens [29–34] .…”

Section: Inflammation Oxidative Stress and Dna Damagementioning

confidence: 99%

The role of reactive oxygen species (ROS) and cytochrome P-450 2E1 in the generation of carcinogenic etheno-DNA adducts

2014

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Exocyclic etheno-DNA adducts are mutagenic and carcinogenic and are formed by the reaction of lipidperoxidation (LPO) products such as 4-hydoxynonenal or malondialdehyde with DNA bases. LPO products are generated either via inflammation driven oxidative stress or via the induction of cytochrome P-450 2E1 (CYP2E1). In the liver CYP2E1 is induced by various compounds including free fatty acids, acetone and ethanol. Increased levels of CYP2E1 and thus, oxidative stress are observed in the liver of patients with non-alcoholic steatohepatitis (NASH) as well as in the chronic alcoholic. In addition, chronic ethanol ingestion also increases CYP2E1 in the mucosa of the oesophagus and colon. In all these tissues CYP2E1 correlates significantly with the levels of carcinogenic etheno-DNA adducts. In contrast, in patients with non-alcoholic steatohepatitis (NASH) hepatic etheno-DNA adducts do not correlate with CYP2E1 indicating that in NASH etheno-DNA adducts formation is predominately driven by inflammation rather than by CYP2E1 induction. Since etheno-DNA adducts are strong mutagens producing various types of base pair substitution mutations as well as other types of genetic damage, it is strongly believed that they are involved in ethanol mediated carcinogenesis primarily driven by the induction of CYP2E1.

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“…The combination of carbon-centered radicals and copper is attracting growing attention in organic synthesis for transformations such as alkylations [5] including trifluoromethylations [6], atom transfer radical additions (ATRA) [7,8] and cyclizations [9], C-H bond oxidative functionalizations [10,11] including fluorinations [12], and alkene difunctionalizations [13], to name just a few examples. Carbon-centered radicals that may be generated in the presence of copper complexes are also relevant in biochemistry [14][15][16][17]. Of even greater interest to us, copper is the champion, in terms of flexibility, ease of implementation and large-scale production potential, as metal mediator for the controlled polymerization of a wide variety of monomers by the radical mechanism known as atom transfer radical polymerization (ATRP) [18].…”

Section: A Introductionmentioning

confidence: 99%

The interaction of carbon-centered radicals with copper(I) and copper(II) complexes*

Ribelli

Matyjaszewski

Poli

2018

Journal of Coordination Chemistry

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Although alkylcopper(I) reagents are widespread, compounds containing alkyl ligands on Cu II or Cu III are much less common. Such complexes, however, are generated as transient species when carbon-center radicals add to Cu I or Cu II complexes, respectively, and appear to be involved in several copper-catalyzed organic transformations. A few organocopper(II) and organocopper(III) complexes were found sufficiently robust to allow isolation and full characterization. This article reviews the reactivity of carbon-centered radicals with Cu I and Cu II ions, both in aqueous and non-aqueous environments, with focus on the importance of the resulting organocopper species on atom transfer radical polymerization and on copper-catalyzed radical termination.

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Role of Nitrative DNA Damage in Inflammation‐Related Carcinogenesis

Cited by 8 publications

References 119 publications

Multi-walled carbon nanotube induces nitrative DNA damage in human lung epithelial cells via HMGB1-RAGE interaction and Toll-like receptor 9 activation

Multi-walled carbon nanotube induces nitrative DNA damage in human lung epithelial cells via HMGB1-RAGE interaction and Toll-like receptor 9 activation

The role of reactive oxygen species (ROS) and cytochrome P-450 2E1 in the generation of carcinogenic etheno-DNA adducts

The interaction of carbon-centered radicals with copper(I) and copper(II) complexes*

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