Tsujiuchi Toshifumi, Nakae Dai, Konishi Yoichi
Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunin-cho, Shinjuku-ku, Tokyo 169-0073, Japan.
Exp Toxicol Pathol. 2014 Mar;66(2-3):81-8. doi: 10.1016/j.etp.2013.11.006. Epub 2013 Dec 27.
N-Nitrosobis(2-hydroxypropyl)amine (BHP) was first synthesized by Krüger et al. (1974), and has been shown to primarily induce pancreatic duct adenocarcinomas by a subcutaneous injection in Syrian hamsters. By contrast, the carcinogenic effect of BHP has been indicated at the different target organs in rats, namely the lung. When rats are received by an oral administration of BHP in drinking water for 25 weeks, a high incidence of lung carcinomas are induced, which include adenocarcinomas, squamous cell carcinomas and combined squamous cell and adenocarcinomas. So many similarities are observed in terms of not only histological appearances but also gene alterations between human and BHP-induced rat lung cancers. Moreover, the step by step development of lung lesions, from preneoplastic lesions to cancers in rat lung carcinogenesis by BHP offers a good model to investigate the mechanisms underlying the pathogenesis of lung cancers. Because data for genetic and epigenetic alterations have indeed been accumulated during the BHP-induced rat lung carcinogenesis, we will introduce them in this review and hence demonstrate that this lung carcinogenesis model provides a useful opportunity for the research on the pathogenesis of lung cancers of both humans and rats.
N-亚硝基双（2-羟丙基）胺（BHP）最早由克鲁格等人于1974年合成，通过皮下注射已被证明主要在叙利亚仓鼠中诱发胰腺导管腺癌。相比之下，BHP在大鼠的不同靶器官（即肺）中已显示出致癌作用。当大鼠通过饮用含BHP的水口服给药25周时，会诱发高发病率的肺癌，包括腺癌、鳞状细胞癌以及鳞状细胞癌和腺癌的混合癌。在人类和BHP诱导的大鼠肺癌之间，不仅在组织学表现方面，而且在基因改变方面都观察到了许多相似之处。此外，BHP诱导的大鼠肺癌发生过程中，肺病变从癌前病变逐步发展为癌症，为研究肺癌发病机制提供了一个良好的模型。由于在BHP诱导的大鼠肺癌发生过程中确实积累了遗传和表观遗传改变的数据，我们将在本综述中介绍这些数据，从而证明该肺癌发生模型为研究人类和大鼠肺癌的发病机制提供了一个有用的机会。
