Three different activated ras genes in mouse tumours; evidence for oncogene activation during progression of a mouse lymphoma.

Five unrelated mouse tumours have been shown to carry activated transforming genes using the NIH/3T3 transfection assay. Three of these tumours, a T-cell lymphoma, a fibrosarcoma and a macrophage tumour, were found to carry an activated c-Ki-ras gene. A c-Ha-ras gene was shown to be activated in a myeloid leukaemia and a recently identified member of the 'ras' gene family, N-ras, was found to be activated in a lung carcinoma. The T-cell lymphoma, L5178Y-ES, is a more aggressively growing metastatic variant which arose spontaneously from the parental tumour, L5178Y-E. Although DNA from both parental and variant tumours was shown to transfer a genetic marker to recipient cells equally well, only the metastatic variant carried an activated c-Ki-ras gene detectable by transfection. The altered growth behaviour of the L5178Y-ES cells may therefore be the result of the spontaneous activation of the c-Ki-ras gene after the lymphoma cells had already become tumorigenic.