PHOTOCARCINOGENESIS AND SUSCEPTIBILITY TO UV-RADIATION IN THE V-HA-RAS TRANSGENIC TG.AC MOUSE

The v-Ha-ras transgenic Tg.AC mouse line has proven to be a useful mod el for the study of chemical carcinogenic potential. We undertook expe riments designed to study the effect of the physical carcinogen, UV ra diation, on tumorigenesis in this mouse strain. Following a total of t hree exposures on alternating days to a radiation source covering a cu mulative UVR exposure range of 2.6-42.6 kJ per m(2), squamous papillom as developed by 4 wk after initial exposure in a dose-dependent manner , Malignancies developed within 18-30 wk following the initial UVR exp osure and were all diagnosed as squamous cell carcinoma or spindle cel l tumors. In contrast to other mouse stains used in photocarcinogenesi s studies, few p53 mutations were found in Tg.AC malignancies upon pol ymerase chain reaction-single stranded conformational polymorphism ana lysis of exons 4-8 followed by sequencing of suspicious bands; however , all tumors analyzed by in sib hybridization expressed the v-Ha-ras t ransgene. Immunohistochemical analysis of UVR-exposed skin taken 24 h after the last of three exposures (13.1 kJ per m(2) total UVR) showed expression of p53 in hair follicles and in interfollicular epidermis, which indicates that the gene was functional, Thus, although there are some differences between the Tg.AC and other mouse models, these resu lts suggest that the Tg.AC mouse may be a useful model for the study o f acute exposure photocarcinogenesis.