The apparent anticarcinogenic action of lanolin.

In the course of their work on the carcinogenic action of oils and tars on mouse's skin, Twort and Twort (4,5) observed that addition of anhydrous lanolin often led to a reduction in neoplastic response. The inhibitory effect was greater than that obtained with benzene as diluent, and also occurred when lanolin was applied separately to the skin during the intervals between paintings. In view of of this apparently specific inhibition of carcinogenesis, the use of lanolin was subsequently recommended as a preventive against occupational cancer in the mule-spinning industry (6) . A more pronounced inhibition of skin carcinogenesis by anhydrous lanolin was recently reported by Simpson, Carruthers and Cramer (1,2,3) in connection with methylcholanthrene. They found that a 0.3 per cent solution of this carcinogen in lanolin, applied thrice weekly for 14 weeks, was almost completely ineffective in inducing tumors or even in initiating those preliminary changes (epilation, destruction of sebaceous glands, epithelial hyperplasia etc.) which are regularly observed when the carcinogen is applied in benzene. This inhibitory effect was shown not to result from (a) inactivation of the carcinogen by the lanolin (b) the prevention of the carcinogen from reaching the epithelial cells, or (c) failure of the carcinogen to persist long enough in situ. Since the amount of methylcholanthrene applied was calculated to be adequate for carcinogenesis, and since ,~_l~e skin treated with the lanolin solution of the carcinogen, far from becoming resistant, was actually more responsive to subsequent painting with a solution of the carcinogen in benzene (3) , they put forward the tentative hypothesis that "unaltered methylcholanthrene is a sensitizing agent, itself non-carcinogenic, that prepares the skin for subsequent action by metabolic derivatives of the carcinogen, or by substances formed in the tissues as a result of exposure to these metabolic products," with the implication that lanolin specifically interferes with this mechanism. Irrespective of the possible merits of this hypothesis, acceptance of any specificity of action on the part of lanolin would be unjustified until simpler interpretations (based on such physical factors as a sub-threshold concentration of the carcinogen in the tissues) are definitely excluded. When a benzene solution of methylcholanthrene is applied to the skin the benzene evaporates immediately leaving behind the carcinogen dissolved in the minute amounts of scbmn normally present on the skin. The effective concentration of the carcinogen will itherefore be nmch higher than the original concentration in the benzene. But when using a non-volatile solvent such as lanolin, the effective concentration practically corresponds to that of the solution as origin/ally applied. It is hardly to be expected that two solutions of a carcinogen, one in a volatile and the other in a nonvolatile solvent, will elicit the same response, even though the amount of carcinogen applied and the original concentration are the same in both cases. 1 Assuming that the inhibitory action of lanolin were entirely due to this dilution effect, one should expect to find (i) that with higher concentration, of the carcinogen in lanolin the neoplastic response should approximate that obtained in benzene, (ii) that other non-volatile solvents would behave similarly to lanolin, and (iii) that the effect should also be demonstrable with carcinogens other than methylcholanthrene. The following experiments were undertaken to test these ~three possibilities.