Licking as a factor affecting dosage in skin carcinogenesis.

The dose of carcinogen applied to the skin is one of the most important factors determining the ultimate tumor incidence (9, 10). However, the experiment of Calcutt and Powell (3) demonstrated that the effective dose of the carcinogen may be considerably lower than that measured onto the skin. Using fluorimetric methods and a single application of 3 mg. of benzpyrene (0.05 ml. of a 6 per cent solution in acetone or benzene), they showed that 95 per cent of the benzpyrene was licked off the skin within 1-2 hours after the application was made. To study the quantitative distribution of radioactivity following skin application of C14-1abeled carcinogens, Heidelberger and Weiss (7) constructed a cage and a protective device that prevented mice from licking and rubbing the site where the carcinogen had been applied. McCarter, Szerb, and Thompson (9) have determined the tumor yield in mice exposed to various concentrations of carcinogens under controlled conditions of exposure that effectively eliminated the possibility of loss of significant amounts of the carcinogen by licking. Because the phenomenon of licking is difficult to control, this factor has been ignored or assumed to be constant in most experiments in experimental skin carcinogenesis. The present investigation was designed to determine the effects both of the amount of 9,10dimethyl-l,2-benzanthracene (DMBA) applied and of the solvent in which it was dissolved on the quantity of carcinogen removed from the skin by licking. The use of radioactive DMBA of high specific activity permitted quantitative measurements of the recovery of carcinogen from the skin of the back of a mouse treated once with as little as 4 gg. of hydrocarbon.