Multistage chemical carcinogenesis in mouse skin.

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

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 - 1980
Externally publishedYes

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Carcinogens
Polycyclic Aromatic Hydrocarbons
Carcinogenesis
Skin
Epoxy Compounds
Neoplasms
Embryonic Induction
Fluocinolone Acetonide
DNA
Polyamines
Tretinoin
Epidermis
Prostaglandins
Anti-Inflammatory Agents
Steroids
Cell Proliferation
Mutation

ASJC Scopus subject areas

  • Medicine(all)

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.

Multistage chemical carcinogenesis in mouse skin. / Slaga, Thomas J; Fischer, S. M.; Weeks, C. E.; Klein-Szanto, A. J.

In: Current Problems in Dermatology, Vol. 10, 1980, p. 193-218.

Research output: Contribution to journalArticle

Slaga, TJ, Fischer, SM, Weeks, CE & Klein-Szanto, AJ 1980, 'Multistage chemical carcinogenesis in mouse skin.', Current Problems in Dermatology, vol. 10, pp. 193-218.
Slaga TJ, Fischer SM, Weeks CE, Klein-Szanto AJ. Multistage chemical carcinogenesis in mouse skin. Current Problems in Dermatology. 1980;10:193-218.
Slaga, Thomas J ; Fischer, S. M. ; Weeks, C. E. ; Klein-Szanto, A. J. / Multistage chemical carcinogenesis in mouse skin. In: Current Problems in Dermatology. 1980 ; Vol. 10. pp. 193-218.
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