THE SEQUENTIAL ANALYSIS OF CANCER INDUCTION WITH CHEMICALS*

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Abstract
A critical review of some of our current views on how chemicals induced cancer is presented. Emphasis is placed on pathologic processes, rather than on agents and on the many steps that lie between initial exposure to a carcinogen and the appearance of malignant neoplasia. The nature of some of the early steps in carcinogenesis is outlined including the early appearance during initiation of cells resistant to some of the inhibitory effect of carcinogens. This property is considered to be important in the development of cancer in at least one model of carcinogenesis. The essential characteristic of promotion, differential stimulation of proliferation of initiated cells, is discussed along with at least three possible mechanisms for such differential effects of promoting environments. The multistep hypothesis for cancer development is supported by observations of identifiable biochemical and biological properties of different cell populations at some steps. The implications of this for cancer diagnosis, prevention and control are briefly discussed.