Chemopreventive action of dexamethasone and α-tocopherol in oxidative stressed cells

Abstract

Introduction: Recent research indicates a close connection of inflammation and cancer as presumed by Virchow in 1893. The growing understanding of cellular signalling and regulatory pathways reveals multiple links between inflammation and cancer. This study was designed to evaluate the influence of the anti-inflammatory drug dexamethasone and the antioxidant α-tocopherol on oxidative induced DNA damage, a major factor in the development of malignancies. Material and methods: Miniorgan cultures (MOC) of fresh biopsied human nasal mucosa were used to keep cells in their microenvironment and thus to mimic in vivo conditions. MOC were pretreated with dexamethasone and α-tocopherol in different concentrations on 1 or on 5 days before oxidative DNA damage was introduced by hydrogen peroxide. The effect of these substances on DNA damage was evaluated using the alkaline single cell microgel electrophoresis (Comet Assay). Results: Dexamethasone induced slight, but considerable DNA fragmentation by itself. It effectively protected cells from hydrogen peroxide induced DNA damage, leading to a maximum decrease of about 45% when preincubated on 5 days at 20 μM. α-Tocopherol most effectively reduced oxidative DNA fragmentation by about 38% when MOC were pretreated 5 days at 20 μM. Discussion: Our experimental data clearly shows the DNA protective action of dexamethasone and α-tocopherol with regard to oxidatively induced DNA damage, a major pathogenetic factor that inflammation and cancer have in common.