Nitrative DNA damage and Oct3/4 expression in urinary bladder cancer with Schistosoma haematobium infection.

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.

• 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)
• 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

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)