Multistage chemical carcinogenesis in mouse skin.

T. J. Slaga, S. M. Fischer, C. E. Weeks, A. J. Klein-Szanto

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26 Scopus citations

Abstract

Skin tumors in mice can be induced by the sequential application of a subthreshold dose of a carcinogen (initiation phase) followed by repetitive treatment with a noncarcinogenic tumor promoter. The initiation phase requires only a single application of either a direct-acting carcinogen or a procarcinogen which has to be metabolized before being active; it is essentially an irreversible step which probably involves a somatic cell mutation as evidenced by a good correlation between the carcinogenicity of many chemical carcinogens and their mutagenic activities. There is a good correlation between the skin-tumor-initiating activities of several polycyclic aromatic hydrocarbons (PAH) and their ability to bind covalently to epidermal DNA. Results from our laboratory as well as others suggest that "bay region" diol-epoxides are the ultimate carcinogenic form of PAH carcinogens. Potent inhibitors and stimulators of PAH tumor initiation appear to affect the level of the PAH diol-epoxide reacting with specific DNA bases. REcent data suggest that the tumor-promotion stage involves at least 3 important steps: (1) the induction of embryonic-looking cells (dark cells) in adult epidermis; (2) an increased production of epidermal prostaglandins and polyamines; (3) sustained proliferation of dark cells. Retinoic acid specifically inhibits step 2, whereas the anti-inflammatory steroid fluocinolone acetonide is a potent inhibitor of steps 1 and 3. The mechanism and the importance of a specific sequence for each step in chemical carcinogenesis in mouse skin will be discussed in detail.

Original languageEnglish (US)
Pages (from-to)193-218
Number of pages26
JournalCurrent problems in dermatology
Volume10
StatePublished - Dec 1 1980
Externally publishedYes

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ASJC Scopus subject areas

  • Dermatology

Cite this

Slaga, T. J., Fischer, S. M., Weeks, C. E., & Klein-Szanto, A. J. (1980). Multistage chemical carcinogenesis in mouse skin. Current problems in dermatology, 10, 193-218.