Detection of a cellular oncogene in spontaneous liver tumors of B6C3F1 mice.

An active cellular oncogene was demonstrated in hepatocellular neoplasms arising spontaneously in 24-month-old B6C3F1 mice. DNA isolated from the tumorous tissue and transfected into NIH 3T3 cells showed an 82 percent (9 of 11 animals) frequency of foci induction. In contrast, DNA isolated from the surrounding nontumorous hepatic tissue from the same animals and DNA from other 24-month-old B6C3F1 mice without tumors did not cause transformation in the NIH 3T3 cell assay. This strain of mouse is used extensively in carcinogen bioassays, and the observed high frequency of transformation (82 percent, compared to 10 to 20 percent in humans) supports the concept that the B6C3F1 mouse is hypersusceptible to liver tumor development. It also emphasizes the need to further understand the mechanisms of oncogene activation in animals used for long-term studies of toxicity and oncogenicity before evaluating potential human risk.