Carcinogenic comparative study on rasH2 mice produced by two breeding facilities.

CByB6F1-Tg(HRAS)2Jic mice (brand name: rasH2 mouse) are produced by two breeding facilities, CLEA Japan, Inc. (Fuji, Shizuoka, Japan) and Taconic (Germantown, NY, USA), and supplied world wide. To confirm carcinogenic conformity of both mice, a 26-week carcinogenicity test was performed on a total of 120 mice obtained from both facilities under the same protocol and same timing in our facility. All mice were divided into a vehicle (citrate buffer at pH 4.5, 10 ml/kg, single intraperitoneal injection) group and a MNU (N-methyl-N-nitrosourea, 75 mg/kg, single intraperitoneal injection) group. Fifteen mice of each sex were assigned to each group. The survival rate of the vehicle group was maintained at 100% for mice from both facilities at completion of the test. In the MNU group, MNU-induced tumor death occurred from 9 to 12 weeks after administration, and the final survival rate for both facilities was 6.7%. In the pathological examination, only benign tumors of lungs, spleen, forestomach and skin were observed in a few mice in the vehicle group of both facilities. In the MNU group, the incidence of forestomach papilloma/squamous cell carcinoma in mice from both facilities was 100%. The incidences of malignant lymphoma in CLEA Japan mice and Taconic mice were 86.7% and 93.3%, respectively, and no significant difference was observed (Fisher's exact probability test). Although lung adenoma and skin papilloma/keratoacanthoma, which are major MNU induced tumors in this strain, were observed in several mice from both facilities, no significant differences were found. Consequently, carcinogenic conformity of rasH2 mice derived from two breeding facilities was confirmed by the present study.

Ribozyme mediated cleavage of cell-associated isoform of vascular endothelial growth factor inhibits liver metastasis of a pancreatic cancer cell line.

Stromal angiogenesis is an important factor for progression of malignant neoplasms. We used hammerhead ribozymes against vascular endothelial growth factor (VEGF) gene transcripts to down-regulate cell-associated VEGF189 isoform function in the pancreatic cancer cell line MIA PaCa2. MIA PaCa2 transfected with anti-VEGF189 ribozyme did not show any alteration of growth rate under tissue culture. When the transformants were subcutaneously transplanted, tumour volume of the ribozyme-transfected MIA PaCa2 xenografts was significantly smaller (P<0.01). No metastasis of MIA PaCa2 transfected with anti-VEGF189 was apparent, while disabled ribozyme-transfected MIA PaCa2 showed significant liver metastasis (P<0.05). These results suggested that VEGF189 plays an important role in growth and metastatic potential through alteration of angiogenic balance in cancer.