Abstract |
To investigate whether mutant stem cells participate in inflammation-related carcinogenesis, we performed immunohistochemical analysis to examine nitrative and oxidative DNA lesions (8-nitroguanine and 8-oxodG) and a stem cell marker Oct3/4 in bladder tissues obtained from cystitis and bladder cancer patients infected with Schistosomahaematobium (S. haematobium). We also detected the expression of nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS), which lead to 8-nitroguanine formation. The staining intensity of 8-nitroguanine and 8-oxodG was significantly higher in bladder cancer and cystitis tissues than in normal tissues. iNOS expression was colocalized with NF-κB in 8-nitroguanine-positive tumor cells from bladder cancer patients. Oct3/4 expression was significantly increased in cells from S. haematobium-associated bladder cancer tissues in comparison to normal bladder and cancer tissues without infection. Oct3/4 was also expressed in epithelial cells of cystitis patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in S. haematobium-associated cystitis and cancer tissues. In conclusion, inflammation by S.haematobium infection may increase the number of mutant stem cells, in which iNOS-dependent DNA damage occurs via NF-κB activation, leading to tumor development.
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Authors | Ning Ma, Raynoo Thanan, Hatasu Kobayashi, Olfat Hammam, Mohamed Wishahi, Tarek El Leithy, Yusuke Hiraku, El-Karef Amro, Shinji Oikawa, Shiho Ohnishi, Mariko Murata, Shosuke Kawanishi |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 414
Issue 2
Pg. 344-9
(Oct 22 2011)
ISSN: 1090-2104 [Electronic] United States |
PMID | 21951846
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Elsevier Inc. All rights reserved. |
Chemical References |
- 8-nitroguanine
- NF-kappa B
- Octamer Transcription Factor-3
- POU5F1 protein, human
- Guanine
- 8-Hydroxy-2'-Deoxyguanosine
- NOS2 protein, human
- Nitric Oxide Synthase Type II
- Deoxyguanosine
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Topics |
- 8-Hydroxy-2'-Deoxyguanosine
- Animals
- Cell Transformation, Neoplastic
(genetics, metabolism)
- Cystitis
(metabolism, parasitology)
- DNA Damage
- Deoxyguanosine
(analogs & derivatives, biosynthesis)
- Guanine
(analogs & derivatives, biosynthesis)
- Humans
- NF-kappa B
(metabolism)
- Neoplastic Stem Cells
(metabolism)
- Nitric Oxide Synthase Type II
(metabolism)
- Octamer Transcription Factor-3
(metabolism)
- Schistosoma haematobium
- Schistosomiasis haematobia
(genetics, metabolism)
- Urinary Bladder Neoplasms
(metabolism, parasitology)
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