Uddin Md Hafiz, Li Shunyu, Jin Yan, Choi Min-Ho, Jang Ja June, Hong Sung-Tae
Department of Parasitology and Tropical Medicine, Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul 03080, Korea.
Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea.
Korean J Parasitol. 2016 Jun;54(3):281-9. doi: 10.3347/kjp.2016.54.3.281. Epub 2016 Jun 30.
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 mm(3)) from the Cs group was a hepatocellular adenoma and the other (280.6 mm(3)) 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.
华支睾吸虫是一种I类生物致癌物，与胆管癌（CCA）相关。仓鼠是华支睾吸虫介导的CCA的唯一实验模型，但我们需要另一种动物模型。本研究旨在使用C3H/He小鼠，在N-亚硝基二甲胺（NDMA）和双环氯嗪（DC）的共同刺激下，建立华支睾吸虫（Cs）介导的CCA模型。将小鼠分为8组，给予不同组合的Cs、NDMA和DC。6个月后处死小鼠，进行大体和组织病理学检查。在接受2种或更多种药物处理的组（如Cs+NDMA、Cs+DC、NDMA+DC和Cs+NDMA+DC）中，体重显著降低。相比之下，上述组的肝脏重量占体重的百分比增加了4.1%至4.7%。仅在Cs+NDMA组观察到脾脏重量的变化。虽然从增生性变化可明显看出华支睾吸虫感染，但仅回收了1条虫。2只小鼠，1只来自Cs组另1只来自Cs+DC组，出现了肿块形成病变；Cs组的1个肿块（281.2 mm³）为肝细胞腺瘤，Cs+DC组的另一个肿块（280.6 mm³）为囊性肿块（紫癜）。Cs组灰白色结节的发生率较高（42.9%），其次是Cs+NDMA+DC组（21.4%）。Cs+NDMA+DC组的小鼠表现出胆管的过度增殖和纤维化改变。在任何组中均未识别出CCA的特征性变化。总之，C3H/He小鼠在同时受到Cs、NDMA和DC攻击时不会产生CCA，但会出现广泛的纤维化。
