BioReliance Corporation, 14920 Broschart Road Rockville, MD 20850, USA.
Int J Toxicol. 2013 Jan-Feb;32(1):48-57. doi: 10.1177/1091581812471565. Epub 2013 Jan 16.
The Tg.rasH2 mouse is a hemizygous transgenic mouse, approved by regulatory agencies for carcinogenicity assessment. However, the absence of a historical database for the incidence of spontaneous neoplasms has subsequently led to reluctance by some pharmaceutical companies to adopt the use of this short-term carcinogenicity assay. Our laboratory has generated a database summarizing the mortality, body weights, and the incidence of spontaneous tumors in 1420 male and female mice assigned to 26 studies conducted at our facility. In addition, we present the incidence of tumors in positive control mice treated with urethane from these studies. Mortality in the vehicle-treated Tg.rasH2 mouse was low (average of 1% in each study). The most common spontaneous tumors in the Tg.rasH2 mice were alveolar bronchiolar adenoma of the lungs (10.14% in males and 5.77% in females) and hemangiosarcoma of the spleen (3.66% in both males and females). The incidence of all other tumors was generally very low. In the positive control, urethane-treated animals, the incidence of alveolar bronchiolar adenomas and alveolar bronchiolar carcinomas in the lungs was 93.69% and 42.88% in males and 92.43% and 72.79% in females, respectively. In addition, the incidence of splenic hemangiosarcomas in urethane-treated males was 89.18% and 92.25% in females. The 6-month Tg.rasH2 assay is more precise, faster, and more economical than the conventional 2-year mouse assays because of the low incidence of background tumors, very high survival, shorter duration, and the lower number of animals used.
Tg.rasH2 小鼠是一种半合子转基因小鼠，已被监管机构批准用于致癌性评估。然而，由于缺乏自发性肿瘤发生率的历史数据库，一些制药公司后来不愿意采用这种短期致癌性检测方法。我们的实验室已经生成了一个数据库，总结了我们实验室进行的 26 项研究中 1420 只雄性和雌性小鼠的死亡率、体重和自发性肿瘤发生率。此外，我们还介绍了这些研究中用尿烷处理的阳性对照小鼠的肿瘤发生率。载体处理的 Tg.rasH2 小鼠的死亡率很低（每项研究平均为 1%）。Tg.rasH2 小鼠中最常见的自发性肿瘤是肺部的肺泡细支气管腺瘤（雄性为 10.14%，雌性为 5.77%）和脾脏的血管肉瘤（雄性和雌性均为 3.66%）。其他肿瘤的发生率通常非常低。在阳性对照、用尿烷处理的动物中，肺部的肺泡细支气管腺瘤和肺泡细支气管癌的发生率分别为雄性 93.69%和 42.88%，雌性 92.43%和 72.79%。此外，尿烷处理的雄性小鼠脾脏血管肉瘤的发生率为 89.18%，雌性为 92.25%。由于背景肿瘤发生率低、存活率非常高、持续时间短以及使用的动物数量少，6 个月的 Tg.rasH2 检测比传统的 2 年小鼠检测更精确、更快、更经济。
