Characteristics of neoplastic progression and tumor behavior in skin carcinogenesis by different methods: an experimental study.

Characteristics of chemically induced skin tumor formation by different methods were studied in 600 Swiss mice. A large dose of 9,10-dimethylbenz(a)anthracene (DMBA) alone or followed by 12-0-tetradecanoyl-phorbol-13-acetate(tpa) and a small dose of DMBA followed by TPA or DMBA repeatedly induced papillomas in 80--90% of the animals. Of these 44--65% regressed and 11--16% became malignant. Keratoacanthomas, observed mainly in repeated DMBA treated animals, were seen to arise de novo in 1--12% of the animals, or from papillomas, 3--12%, they became malignant in 4--9% of the animals. Squamous cell carcinomas were formed de novo in 1--8% of the animals or from papillomas or keratoacanthomas in 10--14% of the animals. Duration of experiment and degree of malignancy related to size of tumor and level of invasion. It is concluded that tumor formation is a stepwise process, with the different types of treatment affecting different aspects of tumor formation to a varying degree.