Effects of naturally occurring plant phenols on production of reactive oxygen species and DNA damage induced by tumour promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA) in mouse epidermis

Naturally occurring phenolics: protocatechuic, chlorogenic, tannic acids and trihydroxystilbene and resveratrol were shown to inhibit multistage carcinogenesis in animal models, including mouse epidermis. Treatment of mouse skin with tumor promoter 12-Otetradecanoyl phorbol-13-acetate (TPA) may induce ROS production in keratinocytes and skin infiltrating leukocytes. In our study, the effect of these phenolics on intracellular ROS production and DNA damage was examined. ROS were analysed by flow cytometry, while DNA damage by comet assay. Following treatment with TPA (6.8 nmol/mouse) two subpopulations of epidermal cells were identified. Pretreatment of mice with 16 mmol of phenolics decreased ROS production in both subpopulations. The most efficient inhibitors of ROS in whole population of keratinocytes were chlorogenic acid and resveratrol. Tannic acid reduced the most DNA damage induced by TPA treatment. These results suggest that anti-promotional effects of these two plant phenols might be partially explained by the inhibition of TPA-induced inflammation.