Sensitization of Skin by Carcinogenically Inactive Methylcholanthrene to Subsequent Carcinogenesis*

The fact described in the preceding paper (9), tl'tat methylcholanthrene dissolved in anhydrous lanolin fails to produce a carcinogenic effect and does not even induce early skin changes such as epilation, epidermal hyperplasia, destruction of sebaceous glands, and diminution in the calcium and iron content of the epidermis, has been established in 4 experimental series comprising 312 mice. Since examination in ultraviolet light demonstrated that the skin absorbs methylcholanthrene from its solution in lanolin, the absence of the carcinogenic effect cannot be attributed to inadequate absorption. Two other possible explanations suggest themselves to account for this phenomenon. One is that the carcinogen exists in lanolin in a physically or chemically inactive state, and the second, that the skin has undergone a biological alteration in the sense of having become resistant to the carcinogen. In order to investigate this question two experiments have been carried out in which the skin of mice, after having been subjected to prolonged treatment with a lanolin solution of methylcholanthrene, was tested subsequently by applying to it a benzene solution of the carcinogen. The results form the subject matter of this paper. Details of the preliminary treatment with the lanolin solution of methylcholanthrene have already been described (9). The experiments designated here as "A" and "C," which supplied the animals for the subsequent treatment with the benzene solution of the carcinogen, are identical with experiments "A" and "C" of our previous paper, so far as the preliminary treatment with methylcholanthrene in lanolin is concerned. The two experiments were carried out in essentially the same manner. Young female Swiss mice from 2 to ] months old were subjected to 42 applications of a 0.3 per cent solution of methylcholanthrene in anhydrous lanolin. These applications were given 3 times weekly for a period of 14 weeks. The animals,