Induction of Skin Tumors in the Mouse with Minute Doses of 9,10-Dimethyl-l,2-benzanthracene Alone or with Croton Oil*

Tumors have been induced frequently in the laboratory mouse following exposure to the carcinogenic hydrocarbons (6). In many of these studies, the chemicals were applied continuously and at a relatively high concentration. Cramer and Stowell (5) compared the tumorigenic effectiveness of e0-methylcholanthrene when applied continuously or discontinuously to the skin of mice and concluded that skin carcinomas could be produced by less carcinogen if the chemical was applied intermittently, e.g., once every 2-4 weeks. Recently, it was observed in this Laboratory that exposure of strain DBA mice once to 9,10-dimethyl-l,2benzanthracene at a concentration too low to produce skin tumors conditioned the hosts to subsequent applications. Thus, one or more additional paintings, each equivalent to the first and applied at intervals as long as 3 months, resulted in the development of numerous skin tumors (7). While Berenblum (1) first demonstrated the enhancing action of croton oil in skin tumorigenesis when combined with repeated applications of a carcinogen, Mot t ram (9) extended this observation by obtaining skin tumors with one subminimal application of a carcinogen followed by continued treatment with croton oil. In a similar experiment, Berenblum and Shubik (3) concluded that the one subminimal dose of carcinogen "init iated" tumorigenesis and the treatment with croton oil "promoted" development to the visible tumor stage. Although one subminimal dose of carcinogen is sufficient to initiate skin tumorigenesis in the mouse, the actual concentrations of carcinogen employed have been relatively large. In the present study, concentrations of 9,10-dimethyl-l,2-benzanthracene as low as 0.00006 per cent have been tested for initiating action follow-