Association of carcinoma yield with early papilloma development in SENCAR mice

The responsiveness of SENCAR mouse skin to 20 different chemicals with known carcinogenic properties was assessed in initiation/promotion experiments. The purpose of these experiments was to evaluate the extent of false negative responses in mouse skin initiation/promotion protocols and to determine the extent to which early papilloma development can be used to predict the eventual development of malignant tumors. The chemicals were administered as initiators by four different routes: oral, intraperitoneal, subcutaneous, and topical. Following the initiating dose of carcinogen, the animals were subjected to topical applications of 1 microgram 12-O-tetradecanoylphorbol-13-acetate (TPA) 3 times per week for a period of 20 weeks. The yield of papillomas at 24 weeks was selected as a potential predictor of carcinoma yields at 52 weeks following the start of the promotion schedule. Positive responses were observed with only eight of the compounds tested. Where positive results were observed, there was some evidence that the response could depend both qualitatively and quantitatively on the route of administration. However, no route was clearly superior, i.e., different chemicals gave greater responses by different routes. Papilloma yield at 24 weeks following the start of the promotion schedule was clearly related to the development of carcinomas at 52 weeks. No simple linear relationship existed between papilloma yield and carcinoma development, since the number of malignant tumors per papilloma decreased with increasing papilloma yields. The relationship between papilloma and carcinoma yields appeared to be independent of the carcinogen used. These data indicate that there are some limitations in using mouse skin initiation/promotion experiments as the sole basis for identifying substances with carcinogenic activity.(ABSTRACT TRUNCATED AT 250 WORDS)