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Reticuloses and Epidermal Tumors in Hairless Mice after Topical Skin Applications of Cantharidin and Asiaticoside

Institute for General and Experimental Pathology, University of Oslo, Rikshospitalet, Oslo 1, Norway

Cantharidin, a vesicant agent, and asiaticoside, which promotes the healing of skin ulcers, were tested for carcinogenicity by topical applications to the skin of hairless mice. A short-term tetrazolium test indicated that both compounds were weak carcinogens. The compounds were then separately painted twice weekly on the dorsal skin up to about 20 months; some of the mice had previously been initiated with a small dose of 20-methylcholanthrene (MCA). A control group which received only the solvent benzene after MCA initiation was also studied.

Cantharidin acted as a weak but complete carcinogen on the skin, causing carcinomas in 6.3% of the animals. These carcinomas did not appear before about 16 months of observation. Before this, the painted, MCA-initiated animals had a significantly lower number of papillomas of the skin than the corresponding control group with only benzene treatment. It therefore seemed that cantharidin in the early stages of painting was tumor inhibitory, or "anticarcinogenic," possibly due to selective damage of latent tumor cells.

By systematic autopsy it was found that nearly 60% of the MCA-initiated, cantharidin-painted mice had reticuloses or malignant lymphomas, while only about 30% of the corresponding MCA-initiated, benzene or asiaticoside-treated animals had such neoplasms. It is therefore concluded that cantharidin penetrates the skin and promotes the development of tumors in the reticuloendothelial system.

Asiaticoside dissolved in benzene gave an increased yield of papillomas and also 2.5% skin sarcomas of the animals, indicating an effect on the dermis as well.

Received 11/29/71. Accepted 3/29/72.