Photobiological model studies of molecular mechanisms behind UV-induced skin cancer and photo aging

The aim of our work has been to investigate theoretically the molecular basis for the initiating steps in the photoimmunological suppression well as DNA mechanisms. In this work we study systematically these two biochromophores, urocanic acid and DNA, starting from an event of absorption of UV-radiation. DNA can become directly damaged through base oxidation mechanisms and there are several possible photoproducts and strand breaks as a worst case scenario. If the lesioned DNA cannot be prepared before transcription it will lead to mutations and likely to a skin cancer. In parallel, another cascade of processes is initiated after that the epidermal chromophore urocanic acid (deamination product of histidine) which is accumulated in stratum corneum in its trans form but isomerized to cis form upon absorption of UV radiation: This will lead to immunosuppression reactions, connected to UV-induced skin cancer. Also, the photophysics of urocanic acid is linked to production of singlet oxygen connected to photo aging. We have come a long way in our theoretical studies to interpret the extremely complicated photochemistry behind these mechanisms. Also we have studied the effects of polyamines (potential anticancer drugs) on DNA. We use new methods allowing us to follow the excited-state dynamics of these chromophores. We use other modelling, tools based on first principles quantum mechanical models together with accurate computer simulation methods to build a physiologically relevant environment where the photophysics takes place. (author)