Effect of Carcinogenic Dosage and Duration of Exposure on Skin-Tumor Induction in Mice2,3

Abstract

Data are presented to indicate (a) threshold levels, for the induction of benign tumors and for their development to a malignant state, and (b) maximally effective carcinogenic dose levels of benzo[a]pyrene on mouse skin. The threshold dosage of carcinogen is apparently dependent in part upon chronicity of exposure. The reported findings indicate that continuation of the process of skin carcinogenesis is directly dependent on dose level and duration of carcinogenic exposure, as well as on potency of carcinogen. Experimental studies are discussed to support the concept that the malignant state in the process of carcinogenesis is a terminal development in a series of increasingly proliferative reactions of normal cells to a persistent physiologically irreparable state of tissue damage or of homeostatic imbalance. It is suggested that a carcinogenic agent is one that produces a physiologically irreparable state of damage or imbalance. The failure of carcinogen-induced neoplasms to progress to malignancy, if the causative factor is removed in time, re-emphasizes the need for identification and control of carcinogen-induced tissue damage and residual carcinogenic agents in man in order that a practical program of cancer control may be attained.