The effects of dexamethasone on mouse skin initiation and aryl hydrocarbon hydroxylase

Sara Thompson, Thomas J. Slaga

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Mouse epidermis contains a NADPH dependent aryl hydrocarbon hydroxylase (AHH), which is inducible by polycyclic hydrocarbons. The effects of dexamethasone, an anti-inflammatory steroid, on skin carcinogenesis and on mouse epidermal AHH were investigated. Dexamethasone was found to reduce tumor initiation by both 3-methylcholanthrene and 7,12-dimethylbenz(a)anthracene. Dexamethasone applied topically to mice at a dose level of 25 or 75 μg slightly stimulated the AHH activity in mouse epidermis with peaks of 150 or 180% of controls, respectively, at 2 hr and a return to control level by 4 hr. This was followed by a weak inhibition between 4 and 8 hr after treatment with either dose of dexamethasone. Dexamethasone did not inhibit benz(a)-anthracene-induced AHH activity in vitro when added to the assay, even at concentrations greater than equimolar amounts to benzo(a)pyrene. However, if dexamethasone or fluocinolone acetonide were applied topically with 3-methycholanthrene (MC), they inhibited the MC induction of AHH by at least 50% between 4 and 18 hr after simultaneous treatment. The more potent anti-inflammatory steroids, fluocinolone acetonide and fluclorolone acetonide, had a greater inhibitory effect on MC induction of AHH after simultaneous treatment. The mouse skin tumor promoters, croton oil and 12-0-tetradecanoylphorbol-13-acetate, had only a weak stimulatory effect on the AHH activity. The mechanism by which the anti-inflammatory steroids inhibit tumor initiation may be related to their ability to inhibit the metabolism of polycyclic hydrocarbons to their ultimate carcinogenic form(s).

Original languageEnglish (US)
Pages (from-to)363-370
Number of pages8
JournalEuropean Journal of Cancer (1965)
Volume12
Issue number5
DOIs
StatePublished - May 1976
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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