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.
Travis
C C
CC
Center for Risk Management, Oak Ridge National Laboratory, Tennessee 37830, USA.
Zeng
C
C
Nicholas
J
J
D015073:2-Acetylaminofluorene / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D005260:Female; D008113:Liver Neoplasms / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008938:Mitosis / Q000187:drug effects*; D008954:Models, Biological; D016296:Mutagenesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D015073:2-Acetylaminofluorene