Mechanism of NO-mediated oxidative and nitrative DNA damage in hamsters infected with Opisthorchis viverrini: a model of inflammation-mediated carcinogenesis

doi:10.1016/j.niox.2004.08.004

Nitric Oxide

Volume 11, Issue 2, September 2004, Pages 175-183

https://doi.org/10.1016/j.niox.2004.08.004 Get rights and content

Abstract

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.

Section snippets

Chemicals and materials

8-Nitroguanine was purchased from Biolog Life Science Institute (Bremen, Germany). Mouse monoclonal anti-8-oxodG antibody was purchased from Japan Institute for the Control of Aging (Fukuroi, Japan). Rabbit polyclonal anti-iNOS and anti-HO-1 antibodies were purchased from Calbiochem–Novabiochem (Darmstadt, Germany) and Stressgen Biotechnologies (Victoria, BC, Canada), respectively. Alexa 594-labeled goat antibody against rabbit IgG and Alexa 488-labeled goat antibody against mouse IgG were

Change of ALT activity in OV-infected hamsters

Fig. 1 shows the changes of plasma ALT activity. ALT activity in infected hamsters was significantly higher than that in control hamsters from day 14 (P < 0.01) and reached the highest peak on day 21 (P < 0.001). Then ALT activity was rapidly decreased on day 30, but remained at higher level than that of normal hamster until day 90 (P < 0.001).

Specificity of anti-8-nitroguanine antibody

Purified antibody gave a strong immunostaining only on the spot of 8-nitroguanine conjugate (Fig. 2A). The immunoreactivity disappeared only when the antibody

Discussion

This study shows that iNOS expression mediates the simultaneous formation of 8-oxodG and 8-nitroguanine in the nucleus of same inflammatory cells and epithelium of bile ducts in the early phase. Relevantly, Jaiswal et al. [33] have demonstrated that iNOS expression mediates 8-oxodG formation in cultured CHCA cells. In the late phase, both 8-oxodG and 8-nitroguanine were mostly observed in small inflammatory cells, bile duct epithelium and small bile ducts. OV infection induced iNOS expression,

Acknowledgments

This work was supported by Khon Kaen Research Fund in Thailand and Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan.

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Mechanism of NO-mediated oxidative and nitrative DNA damage in hamsters infected with Opisthorchis viverrini: a model of inflammation-mediated carcinogenesis

Abstract

Section snippets

Chemicals and materials

Change of ALT activity in OV-infected hamsters

Specificity of anti-8-nitroguanine antibody

Discussion

Acknowledgments

Arch. Biochem. Biophys.

Mutat. Res.

Mutat. Res.

Mutat. Res.

FEBS Lett.

J. Biol. Chem.

Biochem. Pharmacol.

J. Biol. Chem.

J. Hepatol.

Int. J. Parasitol.

Anal. Biochem.

Biochem. Biophys. Res. Commun.

Cell. Biol. Int.

FEBS Lett.

Toxicol. Appl. Pharmacol.

Free Radic. Biol. Med.

Radical causes of cancer

Nat. Rev. Cancer

Formation of 8-nitroguanine by the reaction of guanine with peroxynitrite in vitro

Carcinogenesis

8-Nitroguanosine formation in viral pneumonia and its implication for pathogenesis

Proc. Natl. Acad. Sci. USA

Base modification and strand breakage in isolated calf thymus DNA and in DNA from human skin epidermal keratinocytes exposed to peroxynitrite or 3-morpholinosydnonimine

Chem. Res. Toxicol.

Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA

Nature

Mutagenesis by apurinic/apyrimidinic sites

Annu. Rev. Genet.