Effects of Tumor Promoters and Steroidal Anti-inflammatory Agents on Skin of Newborn Mice In Vivo and In Vitro2

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Abstract
The phorbol esters 12-O-tetradecanoylphorbol-13- acetate (TPA) and 12-O-hexadecanoylphorbol-13 acetate (HPA) are not only potent tumor promoters but also potent stimulators of epidermal DNA synthesis and ornithine decarboxylase (ODC) activity in adult mice. However, when applied topically to newborn mice, TPA and HPA have essentially no effect on epidermal and dermal DNA synthesis or on epidermal ODC activity. Exposure of primary cultures of newborn mouse epidermal cells to TPA or HPA markedly stimulated both DNA synthesis and ODC activity. The anti-inflammatory steroids dexamethasone and fluocinolone acetonide (FA) were found to be potent inhibitors of tumor promotion and epidermal DNA synthesis in adult mice. However, when applied topically to newborn mice, FA did not inhibit epidermal or dermal DNA synthesis but stimulated it approximately twofold at 48 hours after FA treatment. In primary cultures of epidermal cells from newborn mice, treatment with dexamethasone or FA caused an early stimulation of DNA synthesis followed by a 50% inhibition of DNA synthesis 2–3 days after a 1-hour pulse treatment. Also, DNA synthesis was moderately inhibited when FA was added to primary cultures of dermal fibroblasts. In their reaction to tumor promoters, epidermal cells in culture behaved more like adult than newborn mouse epidermis in vivo, whereas anti-inflammatory steroids gave an intermediate response.