Characterization of an inbred strain of the SENCAR mouse that is highly sensitive to phorbol esters.

An inbred strain of SENCAR mice was developed that is more sensitive to two-stage skin carcinogenesis protocols than the outbred parental stock. These mice, registered as SSIN/UTSP, were compared to the SENCAR in initiation-promotion protocols using the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly for 22 weeks at dose levels of 0.5, 1.0 and 2.0 micrograms. With 0.5 microgram of TPA, the number of papillomas in the SSIN was 3-fold higher than in the SEN-CAR; the tumor incidence was 100 versus 60%, respectively. Similar, although less dramatic, results were found with 1.0 and 2.0 micrograms of TPA. In two-step promotion protocols using TPA twice weekly for 2 weeks and 2 micrograms mezerein twice weekly for 15 weeks the SSIN produced approximately 50% more tumors than the SENCAR at 0.5 microgram of TPA. At 2 micrograms of TPA the tumor response between the two mice was not significantly different. Epidermal hyperplasia was considerably greater in the SSIN at 0.5 microgram of TPA as was ornithine decarboxylase activity. These TPA-sensitive inbred mice should be useful in investigations on the biochemical and genetic factors involved in skin tumor promotion.