Assay of Carcinogenic Potential of Chemicals

Transgenic mice expressing activated oncogens offer considerable potential as rapid andsensitive models to identify and quantify the activities of environmental chemicals that act at one ormore steps in the carcinogenic process. The research will focus on two newly developed lines oftransgenic mice, HK1.ras and HK1.fos, that offer particular promise for the rapid and sensitiveidentification and quantification of epidermal carcinogens. These transgenic lines carry a fusiontransgene consisting of the v-Ha-ras or v-fos oncogenes, driven by a human keratin 1 (HK1) promoter,a regulatory element that limits two different stages in the process of epidermal carcinogenesis:activated ras serving as an initiational event and activated fos operating at the promotional stage. Theproposed research will evaluate the specificity and sensitivity of HK1.ras for chemicals having tumorpromoting activity and HK1.fos for chemicals possessing tumor initiating activity. The studies aredesigned to ascertain the feasibility of developing more rapid and cost effective bioassays forenvironmental carcinogens using the HK1.ras and HK1.fos transgenic mice.