C3H/He Mice as an Incompatible Cholangiocarcinoma Model by <i>Clonorchis sinensis</i>, Dicyclanil and N-Nitrosodimethylamine

Abstract

Clonorchis sinensis is a Group-I bio-carcinogen, associated with cholangiocarcinoma (CCA). The hamster is the only experimental model of C. sinensis-mediated CCA, but we oblige another animal model. The present study intended to develop a C. sinensis (Cs) mediated CCA model using C3H/He mice, co-stimulated with N-nitrosodimethyl-amine (NDMA) and dicyclanil (DC). The mice were divided into 8 groups with different combinations of Cs, NDMA, and DC. Six months later the mice were sacrificed and subjected to gross and histopathological examination. The body weights were significantly reduced among the groups treated with 2 or more agents (eg. Cs+NDMA, Cs+DC, NDMA+DC, and Cs+NDMA+DC). In contrast, liver weight percentages to body weight were increased in above groups by 4.1% to 4.7%. A Change of the spleen weight was observed only in Cs+NDMA group. Though C. sinensis infection is evident from hyperplastic changes, only 1 worm was recovered. T wo mice, 1 from Cs and the other from Cs+DC group, showed mass forming lesions; 1 (281.2 mm3) from the Cs group was a hepatocellular adenoma and the other (280.6 mm3) from the Cs+DC group was a cystic mass (peliosis). Higher prevalence of gray-white nodules was observed in Cs group (42.9%) followed by Cs+NDMA+DC group (21.4%). The mice of the Cs+NDMA+DC group showed hyper-proliferation of the bile duct with fibrotic changes. No characteristic change for CCA was recognized in any of the groups. In conclusion, C3H/He mice produce no CCA but extensive fibrosis when they are challenged by Cs, NDMA, and DC together.

The Overactivation of NADPH Oxidase during Clonorchis sinensis Infection and the Exposure to N-Nitroso Compounds Promote Periductal Fibrosis

“…This may be due to insufficient NDMA dosage or/and its inconsistent uptake through drinking water. The same NDMA subcarcinogenic dose has also been reported in C. sinensis-associated CCA animal models in which NDMA administration alone did not cause any obvious histopathological changes in the livers of hamsters and mice [13,44]. Meanwhile, lesion severity and the levels of p47 phox and p67 phox immunoreactivities in livers of the C. sinensis plus NDMA-infected group were higher compared with the C. sinensis-infected group alone, indicating that they synergistically act on the liver deterioration as well as NOX activation.…”

“…Consistent with this, the histopathologic changes (e.g., hyperplasia, peliosis, and extensive biliary fibrosis) in the livers of Cs plus NDMA mice were found. However, no CCA development was observed [44].…”

TLR2 signal influences the iNOS/NO responses and worm development in C57BL/6J mice infected with Clonorchis sinensis

“…Studies have demonstrated that the strains and genetic background of mice are responsible for the susceptibility to C. sinensis infection. C57BL/6 J mice were believed to have the lowest susceptibility to C. sinensis infection compared with FVB, BALB/c and C3H/He mice [ 20 – 24 ]. In this study, we comparatively analysed the developing processes of C. sinensis and the iNOS/NO responses in TLR2 wild-type and mutant C57BL/6 J mice after the infection.…”

“…Several studies reported that many strains of mice, including FVB/NJ (FVB) [ 20 – 22 ], BALB/c [ 8 , 9 , 20 – 23 ], and C3H/He [ 24 ] are susceptible to C. sinensis . By contrast, C57BL/6 mice are resistant to C. sinensis infection [ 22 , 23 ].…”

Association between cholangiocarcinoma and liver flukes: review of epidemiological studies

“…Также значимыми факторами риска являются первичный склерозирующий холангит / язвенный колит, хронические вирусные гепатиты С и В, носительство вируса Эпштейна -Барр, неалкогольная жировая болезнь печени, холелитиаз и (или) мальформации билиарной системы, отложения рентгеноконтрастных веществ (торотраст) в желчных протоках [27,28]. Существуют ýкспериментальные данные, свидетельствующие о том, что индуктором канцерогенеза в желчных протоках может послужить N-динитрозодиметиламин [29,30].…”