Fluocinolone acetonide: A potent inhibitor of mouse skin tumor promotion and epidermal DNA synthesis

James A. Schwarz, Aurora Viaje, Thomas J. Slaga, Stuart H. Yuspa, Henry Hennings, Ulrike Lichti

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

The relationship between the inhibition of mouse skin tumor promotion and the inhibition of epidermal DNA synthesis by the steroidal anti-inflammatory agent, fluocinolone acetonide (FA), was investigated. Simultaneous doses of either 10, 1, or 0.1 μg of FA and phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), resulted in an almost complete inhibition of promotion, whereas 0.01 and 0.001 μg of FA resulted in inhibition rates of 82% and 15%, respectively. Likewise, simultaneous doses of 10 or 1 μg of fluclorolone acetonide (FCA) and TPA caused a nearly complete inhibition of promotion, whereas 0.1 μg of FCA decreased promotion by 62%. In general, as the dose of both steroids was increased, an increase in the tumor latency period was observed. With the exception of the borderline effect of 0.001 μg of FA, the above doses of FA inhibited epidermal DNA synthesis by at least 60% for a 24-h period. Topical treatment with 10 μg of FA resulted in an almost complete inhibition of DNA synthesis for 6 days. The administration of 10 μg of FA 24 h after TPA treatment brought about a maximal inhibition of DNA synthesis of 65%, as compared with a 98% inhibition in control mice whose DNA synthesis had not been prestimulated. That is, FA was not quite as effective on S-phase cells as on G-1 cells. There appears to be a relationship between the inhibition of tumor promotion and epidermal DNA synthesis.

Original languageEnglish (US)
Pages (from-to)331-347
Number of pages17
JournalChemico-Biological Interactions
Volume17
Issue number3
DOIs
StatePublished - Jun 1977
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology

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