2,4,6-Trihydroxyphenanthrene, a trans-resveratrol photoreaction byproduct: first evidences of genotoxic risk

Resveratrol, a natural product with well-known multiple beneficial effects, has been widely used as a bioactive principle for the development of anti-aging topical phytoproducts. These products are usually applied to skin that is often exposed to solar light for a long time, leading to potentially harmful resveratrol derivatives. In this study we investigated the cytotoxicity and genotoxicity of 2,4,6-trihydroxyphenanthrene (THP), derived from trans-resveratrol photochemical isomerization and electrocyclization. To achieve this goal, we used Caulobacter crescentus as the experimental model for evaluating the colony-forming ability and the SOS response induction of cells exposed to THP. DNA-strand breaks and oxidative damage were assessed by the cell-free pCMut plasmid. The obtained data demonstrated that THP induces a cytotoxic and genotoxic effect of THP even at sub-micromolar concentrations, through a pro-oxidant mechanism leading to DNA damage.