Cutaneous two-stage chemical carcinogenesis

INTRODUCTIONThe induction of cutaneous carcinogenesis in mice by topical administration of chemicals enables the local, systemic, and environmental factors that influence tumor susceptibility, growth, and progression to be studied in the laboratory. Chemical carcinogenesis in mouse skin has been used for several decades, and continues to help in the identification of important molecular and immunological pathways involved in cutaneous malignancy. This protocol describes the two-stage application of chemicals to the skin for the initiation and promotion of cutaneous tumors. In the two-stage model of induction, a single application of the chemical initiator mutagen 7,12-dimethylbenz[a]anthracene (DMBA) is followed by repeated applications of a pro-inflammatory phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA; otherwise known as phorbol 12-myristate 13-acetate [PMA]). Resulting tumors may develop in the form of benign papillomas that regress or progress to SCC, or SCC may arise without an apparent precursor lesion. Thus, two-stage chemical carcinogenesis provides an opportunity to monitor early and late events in cancer development and progression.