The additivity of multiple doses of a liver carcinogen in rats

The temporal pattern and dose-rate dependence of liver cancer in rats fed 2-fluorenylacetamide (2-FAA) was compared to analytical formulas derived from a specific model. The model was based on the idea that carcinogens have two distinct actions on cells: (1) transformation and (2) acceleration of progression. Transformed cells are by definition progressing toward cancer, but their rate of progression may depend on several factors, specifically, the amount of carcinogen. In the experiments the carcinogen was removed from the diet after various times and the rate of tumor progression was estimated from the time of tumor occurrence. The results were consistent with the idea that 2-FAA accelerated the progression of the cancers. The model provides a simple explanation of Druckrey's law in that the temporal occurrence of tumors induced by a carcinogen represents the acceleration of a naturally occurring disease progression.