Active H-ras and N-ras in rat fibrosarcomas induced by 1,6-dinitropyrene.

The activated oncogenes in rat fibrosarcomas induced by subcutaneous injection of 1,6-dinitropyrene (1,6-DNP), an environmental mutagen-carcinogen, were examined by NIH3T3 cell transfection assay and Southern blot analysis. DNAs from two of eleven fibrosarcomas, 1,6-DNP6 and 1,6-DNP9T, induced transformants which contained rat specific repetitive sequences. Three primary transformants, obtained with DNA from 1,6-DNP6, and two secondary transformants of one of these primary transformants tested, contained rat H-ras. DNA from 1,6-DNP9T; a fourth transplant of 1,6-DNP9, also induced transformants. All the primary transformants with DNA from 1,6-DNP9T, and three secondary transformants of one of them, contained rat N-ras. The DNA from the original tumor, 1,6-DNP9, however, did not give any transformants by several transfection assays. Activation of N-ras oncogene during serial transplantations is discussed.