Biological model of ED01 hepatocarcinogenesis

The ED01 bioassay on 2-acetylaminofluorene (2-AAF)-induced hepatocarcinogenesis in BALB/c mice was analyzed using a biologically based, two-mutation model of the oncogenic process. Computer simulations indicate that 2-AAF-induced hepatocarcinogenesis has both genotoxic and promotional components. However, contrary to the current paradigm, we find that the genotoxic component of 2-AAF plays a minor role in its carcinogenicity. The ED01 hepatocarcinogenicity can be explained almost entirely to result from the promotional influence of 2-AAF on an existing pool of spontaneously initiated cells.