title: 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.affiliation: Faculty of Health Science, Suzuka University of Medical Science, Suzuka, Mie, Japan.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.forename: Raynoo
authors.initials: R
authors.lastname: Thanan
authors.forename: Hatasu
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Olfat
authors.initials: O
authors.lastname: Hammam
authors.forename: Mohamed
authors.initials: M
authors.lastname: Wishahi
authors.forename: Tarek
authors.initials: T
authors.lastname: El Leithy
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hiraku
authors.forename: El-Karef
authors.initials: el-K
authors.lastname: Amro
authors.forename: Shinji
authors.initials: S
authors.lastname: Oikawa
authors.forename: Shiho
authors.initials: S
authors.lastname: Ohnishi
authors.forename: Mariko
authors.initials: M
authors.lastname: Murata
authors.forename: Shosuke
authors.initials: S
authors.lastname: Kawanishi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D003556:Cystitis / Q000378:metabolism / Q000469:parasitology*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D006147:Guanine / Q000031:analogs & derivatives / Q000096:biosynthesis; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D012548:Schistosoma haematobium; D012553:Schistosomiasis haematobia / Q000235:genetics / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000469:parasitology*
chemical_list: C095838:8-nitroguanine; D016328:NF-kappa B; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D006147:Guanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D003849:Deoxyguanosine