Mechanism of NO-mediated oxidative and nitrative DNA damage in hamsters infected with Opisthorchis viverrini: a model of inflammation-mediated carcinogenesis.
Inflammation mediated by infection is an important factor causing carcinogenesis. Opisthorchis viverrini (OV) infection is a risk factor of cholangiocarcinoma (CHCA), probably through chronic inflammation. Formation of 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and expression of inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) were assessed in the liver of hamsters infected with OV. We newly produced specific anti-8-nitroguanine antibody without cross-reaction. Double immunofluorescence staining revealed that 8-oxodG and 8-nitroguanine were formed mainly in the same inflammatory cells and epithelium of bile ducts from day 7 and showed the strongest immunoreactivity on days 21 and 30, respectively. It is noteworthy that 8-oxodG and 8-nitroguanine still remained in epithelium of bile ducts on day 180, although amount of alanine aminotransferase activity returned to normal level. A time course of 8-nitroguanine was associated with iNOS expression. Furthermore, this study demonstrated that HO-1 expression and subsequent iron accumulation may be involved in enhancement of oxidative DNA damage in epithelium of small bile ducts. In conclusion, nitrative and oxidative DNA damage via iNOS expression in hamsters infected with OV may participate in CHCA carcinogenesis.
Pinlaor
Somchai
S
Department of Environmental and Molecular Medicine, Mie University School of Medicine, Mie 514-8507, Japan.
Hiraku
Yusuke
Y
Ma
Ning
N
Yongvanit
Puangrat
P
Semba
Reiji
R
Oikawa
Shinji
S
Murata
Mariko
M
Sripa
Banchob
B
Sithithaworn
Paiboon
P
Kawanishi
Shosuke
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D018281:Cholangiocarcinoma / Q000209:etiology* / Q000469:parasitology / Q000473:pathology; D006224:Cricetinae; D004249:DNA Damage / Q000502:physiology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006147:Guanine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D051547:Heme Oxygenase-1; D007249:Inflammation / Q000150:complications; D008099:Liver / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009889:Opisthorchiasis / Q000150:complications* / Q000235:genetics / Q000473:pathology; D009891:Opisthorchis; D010084:Oxidation-Reduction
C095838:8-nitroguanine; D009569:Nitric Oxide; D006147:Guanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D003849:Deoxyguanosine