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URETHANE has been shown to induce the initiating phase of skin carcinogenesis in mice, not only when applied locally (Graffi, Vlamynch, Hoffmann, and Schulz, 1953; Salaman and Roe, 1953; Roe and Salaman, 1954; Berenblum and Haran, 1955b), but also when administered by mouth (Haran and Berenblum, 1956). The fact that urethane (ethyl carbamate) has a relatively simple chemical structure, is water-soluble, is itself non-carcinogenic for skin epithelium in the mouse, and does not even elicit epithelial hyperplasia, or any other demonstrable evidence of skin irritation-so constant a feature of other initiating agents or skin carcinogens, renders it all the more attractive a tool for the study of the nature of initiating action. Before one could effectively exploit urethane for this purpose, some quantitative data were needed about the conditions under which its systemic initiating action operated. The results of such a quantitative study, presented here, are concerned with (a) variations in total dose of urethane, given once only by mouth; (b) different numbers of urethane feedings, totalling the same overall dose; (c) different routes of administration of urethane, e.g. by mouth, intraperitoneally, subcutaneously, and topically applied to the skin; and (d) variations in the interval between the end of initiating action (urethane by mouth) and the commencement of promoting action (croton oil applied repeatedly to a small area of skin).

Mortality Rates for Cancer of Urinary Bladder in Various Countries