Phenotypic Monitoring of rasH2 Mice

rasH2 mice are a well-accepted model for assessing carcinogenic risk of pharmaceuticals. They are are produced at Taconic (Germantown, NY, USA) and CLEA Japan (Fuji, Shizuoka, Japan). In order to monitor the biological equivalence and stability of the phenotype of rasH2 mice, mainly carcinogenic susceptibility, produced at these two locations, we have periodically compared the carcinogenic response of these mice to the standard positive control compound N-methyl-N-nitrosourea (MNU).

No difference was observed in carcinogenic susceptibility of rasH2 mice produced by Taconic and CLEA Japan.

  • Thirty male and female rasH2 mice introduced from Taconic and CLEA Japan at 6 weeks of age were divided into 15 mice / group. The mice were given a single intraperitoneal injection of vehicle or 75 mg/kg MNU.
  • The animals were observed until 26 weeks after vehicle or MNU administration. When they became moribund, mice were necropsied under anesthetized condition. Weight of thymus, liver, spleen and lung were measured at necropsy.
  • Histopathological studies were performed for all organs to compare carcinogenic susceptibility of rasH2 mice derived from the two facilities.
  • The results of present study were compared to the results obtained in 2006 to investigate long-term biological stability of the phenotype.
In present study, rasH2 mice produced by Taconic were slightly smaller than mice produced by CLEA Japan.figure 2
Body weight gain of rasH2 mice produced by Taconic and CLEA Japan
Survival rate of MNU treated female rasH2 mice from Taconic in 2013 was shorter than mice from CLEA Japan.figure 3
Survival rate of rasH2 mice produced by Taconic and CLEA Japan
Spleen and thymus weights of MNU treated mice were heavier than that of vehicle treated mice for both colonies.figure 4
Organ weights of rasH2 mice produced by Taconic and CLEA Japan
In full-volume monitoring performed in 2006 and 2013, no significant difference was observed between the mice from Taconic and CLEA Japan for the incidence of major MNU-induced tumors such as fore stomach papillom/carcinoma, malignant lymphoma, skin papilloma and lung adenoma, except for male lung adenoma in 2013 (Table 1).

Table 1. Incidence of neoplasm after MNU administration in full-volume monitoring performed in 2006 and 2013
(Click the charts below for full size images)
rash2-male.png
rash2-female.png
Most of non-neoplastic lesions observed in present study were similar to the background data (Data not shown).
Although rasH2 mice produced by Taconic were smaller than mice produced by CLEA Japan in present study, they showed similar clinical findings during the study.

Survival curve after MNU treatment in female produced by Taconic in present study was shorter than that of female from CLEA Japan, but they started to become moribund or died simultaneously and final survival rates were similar.

Considering these results, we concluded that no difference was recognized in carcinogenic susceptibility of rasH2 mice produced by Taconic and CLEA Japan and their carcinogenic susceptibility have been well maintained since the ILSI/HESI International Act. project.
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