The Importance of Differential Consideration of the Stages of Carcinogenesis in the Evaluation of Cocarcinogenic and Anticarcinogenic Effects

This communication is an attempt to clarify and extend the concepts dealing with certain extrinsic or intrinsic factors that augment or retard .darcinogenesis. Before discussing carcinogenesis it may be helpful to differentiate again between carcinogenesis and the subsequent growth of a tumor. 1 Carcinogenesis implies the initiation of a neoplasm by a tumor-producing agent acting on normal tissue. Once the tumor is of microscopic size, even before it is perceptible on gross examination, carcinogenesis can be assumed to have been completed; the multiplication of the new tumor cells represents growth. The differentiation between genesis and growth is based both on morphological considerations and on the experimental observation of factors that encourage or inhibit carcinogenesis, while they have little or no influence on the growth of the tumor. Thus it is of experimental and possibly of clinical importance to distinguish between the genesis of a neoplasm from normal tissue, and the growth of such a tumor, or of tumor implants. Nevertheless one still finds references in the literature to the effects of a particular agent or procedure, without regard to the difference between genesis and growth. A parallel situation, dependent on the recognition of distinct stages in carcinogenesis itself, has developed more recently. On the basis of experimental data and suggestions by Rous and his associates (30, 36), Berenblum (10), Tannenbaum (44), and the earlier work of others (19-21), and for experimental and possibly clinical purposes, it appears desirable to consider differentially the recognizable stages of carcinogenesis. Stages of carcinogenesis.--In extensive morphological