Studies on in vivo evaluation system of treatment for cancer prevention and progression using cancer prone gene-engineered mice

我们研究了利用致癌基因工程小鼠建立肿瘤预防和进展治疗的体内评价系统。我们一直在研究利用携带人类原型H-ras癌基因的rasH2转基因小鼠进行致癌性测试的模型。在这项研究中，我们建立了乌拉坦诱导的肺癌模型，致瘤性非常快。我们将这种易患癌症的小鼠系统应用于评估用于癌症预防或预防癌症进展的药物或治疗方案，如化学预防。rasH2小鼠被注射乌拉坦诱发肺癌。在乌拉坦注射后或注射前，将IL-6相关基因复合体(IL-6、IL-6受体和gp130)攻击小鼠。在乌拉坦和氨基甲酸乙烯酯(Vc，乌拉坦的近端致癌物)诱发的小鼠肺肿瘤中，导入人H-ras基因的突变分析表明，IL-6相关基因复合体具有化学预防作用。结果表明，几乎所有肿瘤都存在H-ras基因第61位密码子突变。这些结果表明，转基因61位密码子的点突变在VC和氨基甲酸乙酯诱发的rasH2小鼠肺癌的发生中起重要作用。

We studied to establish in vivo evaluation system of treatment for cancer prevention and progression using cancer prone gene-engineered mice. We have been studying carcinogenicity testing model using rasH2 transgenic mice harboring human prototype H-ras oncogene. In this study, we established urethane-induced lung cancer model with very rapid tumorigenicity. We applied this cancer prone mice system for evaluation of drug or treatment protocol for cancer protection or prevention of cancer progression such as chemoprevention.The rasH2 mice were injected urethane to induce lung tumor. After or before urethane injection, IL-6 related gene complex (IL-6, IL-6 receptor and gp130) was challenged into the mice. The incidence of lung tumor formation in the urethane injected rasH2 mice was clearly reduced, meaning the IL-6 related gene complex has chemoprevention effects.The mutational analyses of introducing human H-ras were performed in the lung tumor which induced by urethane and vinylcarbamate (VC, proximal carcinogen of urethane). The results showed almost all tumors had mutation at the 61st codon of H-ras. These results suggested that point mutations at codon 61 of the transgene play an important role in the carcinogenesis of VC- and urethane- induced lung tumors in rasH2 mice.