Chemopreventive action of dexamethasone and alpha-tocopherol in oxidative stressed cells.
BACKGROUND
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 alpha-tocopherol on oxidative induced DNA damage, a major factor in the development of malignancies.


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 alpha-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 microM. alpha-Tocopherol most effectively reduced oxidative DNA fragmentation by about 38% when MOC were pretreated 5 days at 20 microM.


CONCLUSIONS
Our experimental data clearly shows the DNA protective action of dexamethasone and alpha-tocopherol with regard to oxidatively induced DNA damage, a major pathogenetic factor that inflammation and cancer have in common.
Baumeister
P
P
Department of Otolaryngology and Head and Neck Surgery, Ludwig-Maximilians-University, Marchioninist, 15, 81377 Munich, Germany. philipp.baumeister@med.uni-muenchen.de
Korn
G
G
Berghaus
A
A
Matthias
C
C
Harréus
U
U
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D020552:Comet Assay; D004249:DNA Damage; D053938:DNA Fragmentation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D009924:Organ Culture Techniques; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D024502:alpha-Tocopherol / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D016588:Anticarcinogenic Agents; D000975:Antioxidants; D003907:Dexamethasone; D006861:Hydrogen Peroxide; D024502:alpha-Tocopherol