Promotion and Cocarcinogenesis

Abstract

In experimental animals, tumors can be induced according to different protocols. Solitary carcinogenesis involves the application/administration of only one carcinogenic agent, given either once in a single high dose or repeatedly in several small doses. Solitary carcinogens, either as such or after metabolic transformation, can induce tumors by themselves, without the cooperative action of any other chemical agent. Generally, solitary carcinogens bind covalently to DNA and tend to induce DNA repair—they are genotoxic. A protocol of multistage carcinogenesis, in contrast, is based on the cooperative action of two or more different agents, each of which is unable by itself to induce the development of tumors when the experimental conditions are carefully controlled. Multistage models of carcinogenesis which have been developed for various animal species and tissues (1,2) provide methodological tools for mechanistic investigations, since tumor development is a complex process that can be subdivided into stages so as to yield to analysis on the cellular and molecular level. The operational concepts, initiation and promotion, are based historically on observations made in the framework of the two-stage mouse skin carcinogenesis protocol.