Analysis of Ras Gene Mutations in Main Spontaneously-occurring Non-epithelial Tumors of B6C3F1 Mouse.

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The B6C3F1 (C57BL/6 × C3H/He) mouse has commonly been used for various chronic toxicity and carcinogenicity studies. This mouse develops various types of spontaneous tumors during its lifetime. The incidence of ras gene mutation has been reported in tumors of various epithelial tissues including the liver, lung, and Harderian gland of the B6C3F1 mice. However, there are few reports on the frequency of ras activation in non-epithelial tumors in spite of their high incidence similar to that of epithelial tumors. We examined ras gene mutations in 114 non-epithelial tumors (hemangioendothelial cell tumors, malignant lymphomas, and histiocytic sarcomas), generated spontaneously in B6C3F1 mice by non-RI single strand conformation polymorphism analysis and direct sequencing of DNA, which was isolated from paraffin-embedded sections and amplified by polymerase chain reaction. Only seven non-epithelial tumors in the B6C3F1 mice contained mutation of the H-ras codon 61, all of which were C to A transversion (CAA → AAA). The present studies suggest that activation of the ras gene is involved only a little in occurrence of the primary spontaneous non-epithelial tumors and that the pathways other than ras gene activation lead to the development of most non-epithelial tumors in the B6C3F1 mouse.
日本毒性病理学会の論文