Rogers Arlin B, Houghton JeanMarie
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
Methods Mol Biol. 2009;511:267-95. doi: 10.1007/978-1-59745-447-6_11.
Animal models are necessary to reproduce the complex host, microbial and environmental influences associated with infectious carcinogenesis of the digestive system. Today, mouse models are preferred by most researchers because of cost efficiencies, rapid reproduction, choice of laboratory reagents, and availability of genetically engineered mutants to study specific gene functions in vivo. Mouse models have validated the once-provocative hypothesis that Helicobacter pylori infection is a major risk factor for gastric carcinoma, dispelling early skepticism over the pathogenic nature of this organism in the human stomach. Enterohepatic Helicobacter spp. induce inflammatory bowel disease and colorectal carcinoma in susceptible mouse strains, permitting study of host immunity and microbial factors at the cellular and molecular level. H. hepaticus is the only proven infectious hepatocarcinogen of mice and has been used to explore mechanisms of inflammation-associated liver cancer as seen in human chronic viral hepatitis. For example, this model was used to identify for the first time a potential mechanism for male-predominant liver cancer risk independent of circulating sex hormones. Helicobacter-based mouse models of digestive system carcino-genesis are used to investigate the basic biology of inflammation-associated human cancers and to evaluate therapeutic interventions at the discovery level. Because of exciting advances in genetic engineering of mice, in vivo imaging, and system-wide genomics and proteomics, these models will provide even more information in the future. This chapter introduces the mouse as a model species; summarizes important models of inflammation-associated cancer incited by murine Helicobacter infection; and describes methods for the collection, sampling, and histologic grading of mouse digestive system tissues.
动物模型对于重现与消化系统感染性致癌作用相关的复杂宿主、微生物和环境影响是必要的。如今，由于成本效益、繁殖速度快、实验室试剂的选择以及可利用基因工程突变体在体内研究特定基因功能，大多数研究人员更喜欢使用小鼠模型。小鼠模型证实了曾经颇具争议的假说，即幽门螺杆菌感染是胃癌的主要危险因素，消除了早期对该生物体在人类胃部致病性的怀疑。肝肠螺杆菌属在易感小鼠品系中诱发炎症性肠病和结直肠癌，从而能够在细胞和分子水平研究宿主免疫和微生物因素。肝螺杆菌是唯一经证实的小鼠感染性肝癌致癌物，已被用于探索人类慢性病毒性肝炎中所见的炎症相关肝癌的发病机制。例如，该模型首次确定了一种与循环性激素无关的男性为主的肝癌风险潜在机制。基于螺杆菌的小鼠消化系统致癌模型用于研究炎症相关人类癌症的基础生物学，并在发现层面评估治疗干预措施。由于小鼠基因工程、体内成像以及全系统基因组学和蛋白质组学方面令人兴奋的进展，这些模型未来将提供更多信息。本章介绍小鼠作为模型物种；总结由鼠螺杆菌感染引发的炎症相关癌症的重要模型；并描述小鼠消化系统组织的收集、采样和组织学分级方法。
