An approach to the development of a short-term whole-animal bioassay to distinguish initiating agents (incomplete carcinogens), promoting agents, complete carcinogens, and noncarcinogens in rat liver.

With increased knowledge of the stages of initiation and promotion in the natural history of neoplastic development and the multiple observations that such stages are likely to be ubiquitous in the natural history of all histogenetic types of neoplasms, it is becoming increasingly important to distinguish chemical agents that act selectively during one or the other of these stages. Utilizing data obtained from the published literature as well as further observations, the experimental findings reported in this paper serve to indicate an approach to the development of a short-term whole-animal bioassay capable of distinguishing agents that act at one or the other or both of the stages of initiation and promotion in rat liver. Because of the tissue specificity for both complete carcinogens and promoting agents, this bioassay system is not likely to identify the initiating and promoting capabilities of all carcinogenic agents and thus at present is not designed to replace the standard chronic bioassay systems. However, in view of the diverse metabolic capabilities of hepatic tissue, the system proposed in this paper may represent a model capable of distinguishing the stages of carcinogenesis at which many, if not most, specific carcinogenic chemicals exert their primary action.