7,12-Dimethylbenz[a]anthracene/12-O-tetradecanoyl-phorbol-13-acetate-mediated skin tumor initiation and promotion in male Sprague-Dawley rats.

In contrast to a previous report by Shubik and in accordance with a pilot study from our laboratory with female rats, the 2-stage skin carcinogenesis experiment could be successfully accomplished in male Sprague-Dawley rats. Male animals of this species are better suited for this long-term experiment since, under the conditions used, females are very sensitive to mammary gland tumor formation and show a drastically reduced survival time. A broad spectrum of tumors of epidermal origin could be induced by topical initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetra-decanoyl-phorbol-13-acetate (TPA) as promoter. The tumors were not only localized in the interfollicular epidermis but to a large extent also in the epidermal appendages. More importantly, the DMBA - TPA treatment led to the development of a variety of tumors of the connective tissue and the angiofibrous matrix. The incidence of these tumors was almost comparable to that found for epidermal tumors. In some animals we observed up to 12 histologically different tumors. Compared to the mouse, the tumor incidence in organs other than the skin was definitely lower. Ethyldiazoacetate (EDA), a substance which has been shown to induce skin tumors when administered i.v. to rats, was tested with regard to its initiating capacity. The combination EDA-TPA led to a skin tumor spectrum comparable to that produced by DMBA-TPA. However, the survival time of the EDA-TPA treated animals was significantly higher than those exposed to DMBA-TPA. EDA, therefore, seems to be a suitable alternative to DMBA for systemic initiation of skin tumors.