Figure 1. Two-stage model of skin carcinogenesis in mice.

During initiation, topical application of a sub-carcinogenic dose of a mutating agent induces mutations in target genes in keratinocyte stem cells. Repeated topical application of a promoting agent begins two weeks after initiation and continues for the duration of the study. Papillomas begin to arise after approximately 6–12 weeks of promotion and a fraction begin to convert to SCC after approximately 20 weeks. Representative H&E stained sections of normal skin, hyperplastic skin, a papilloma, and a SCC are presented. All mice were handled in accordance with institutional and national regulations. This figure is a modification of a previously published figure¹³³.