Abstract
Evidence that tumorigenesis is a multistage process first emerged from experiments showing that wounding of skin previously treated with coal tar resulted in tumor formation at the wound site (1). Subsequent experiments in which physical trauma was replaced by the application of chemical irritants not intrinsically tumorigenic yielded similar results (2,3). These observations were codified by Rous, who coined the terms “initiation” and “promotion” to denote respectively (a) the production of potentially tumorigenic cells by limited carcinogen treatment and (b) the completion of the neoplastic transformation resulting from subsequent treatment with any of a wide variety of noncarcinogenic irritants and proliferative stimuli (3).
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