Renal Tumors in 26-Week Tg.Rash2 Mice Carcinogenicity Studies

Abstract

We report renal tubular adenomas and a carcinoma in 26-week Tg.rasH2 mouse carcinogenicity studies, which have not been reported to date either at our facility or in other published data. However, during the year 2014, renal tubular tumors were present in 4 studies conducted at our facility. Because of their morphological similarity to the amphophilic-vacuolar (AV) phenotypic variant of renal tubule tumors noted in Sprague-Dawley and Fischer 344 rats, which are thought to be familial, as well as the genetic homogeneity of Tg.rasH2 mice, we tracked the parents of these mice with tumors in each study. The origin of these tumors could not be traced back to any of the parents or even an animal barrier, and these tumors were not attributed to the vehicle or test article. Although the exact mechanism of tumorigenesis was not known, based on the available information, the development of renal tumors in these mice was considered random and spontaneous. KeywordsTg.rasH2, renal tumors, renal tubular adenomas, renal tubular carcinoma, historical incidence, carcinogenicity studiesThe 2-year rodent carcinogenicity assays involving conventional rats and mice have been conducted for over 3 decades. As an alternative to the 2-year rodent carcinogenicity bioassays, 26-week short-term carcinogenicity bioassays were approved using genetically modified mouse strains, including Tg.rasH2 (International Conference on Harmonisation 1998). The Tg.rasH2 model, which can be used for both genotoxic and nongenotoxic compounds, has gained popularity and its use has increased over the years, and currently more than 75% of mouse carcinogenicity studies are conducted in Tg.rasH2 mice (Jacobs and Brown 2015).

Lung Tumor Induction by 26-week Dermal Application of 1,2-Dichloroethane in CB6F1-Tg rasH2 Mice

“…Moreover, another study using acetone as one of the controls did not observe renal cell carcinoma in the acetone group after dermal application of acetone to rasH2 mice for 26 weeks (Urano et al 2007). Recently, Paranjpe et al (2016) reported that the development of renal cell tumors in rasH2 mice is random and spontaneous. Therefore, all neoplastic lesions observed in the male acetone group were considered spontaneous, and dermal applications of acetone in our 26-week carcinogenicity study using rasH2 mice did not exhibit carcinogenic potential.…”