Drug-induced enhancement of hepatic tumorigenesis

Epidemiological evidence suggests that the human population is exposed to environmental agents that increase the risk of cancer. The two-stage or initiation-promotion model of tumorigenesis raises the possibility that such environmental agents may comprise both carcinogens and substances that are not carcinogens themselves but instead enhance the tumorigenic effects of brief exposures to low levels of carcinogens. Results are reported from studies on rats that show that dietary phenobarbital enhances liver tumorigenesis initiated by the prior feeding of the carcinogen, 2-acetylaminofluorene (AAF). Phenobarbital is a well known stimulator of liver growth but its effects are reversible, and thus far there is no unequivocal evidence that phenobarbital is tumorigenic. Other agents that influence liver growth and metabolism to varying degrees were also tested.