Hypoxia potentiates ultraviolet A-induced riboflavin cytotoxicity

Flavins are thought to be important chromophores for chronic photo-induced skin injury, but the mechanism is not well known. We have reported that the primary cytotoxicity remaining in ultraviolet A-irradiated riboflavin solu tion is attributable to hydrogen peroxide. Because the dermis is more hypox ic than the atmosphere, we investigated the cytotoxicity of riboflavin solu tion during and after ultraviolet A irradiation under hypoxia. Riboflavin s olution showed stronger cytotoxicity during irradiation under hypoxia than under air. Riboflavin solution that had been irradiated under hypoxia at lo wer ultraviolet A doses showed stronger cytotoxicity and contained more hyd rogen peroxide than solution irradiated under air at the same doses. At hig her ultraviolet A doses, however, the cytotoxicity and hydrogen peroxide qu antity were similar in riboflavin solutions irradiated under different oxyg en conditions. The effect of a singlet oxygen quencher, sodium azide, on th e induction of cytotoxicity and production of hydrogen peroxide by ultravio let A irradiation of riboflavin solution was examined. The presence of sodi um azide in the solution during ultraviolet A irradiation suppressed the cy totoxicity and hydrogen peroxide production to similar levels at various ul traviolet A doses regardless of oxygen conditions. At the maximum suppressi on by sodium azide, hydrogen peroxide production decreased to 10% of the un suppressed production. About 40% of the oxygen molecules of hydrogen peroxi de produced was thought to be derived from oxygen dissolved in the riboflav in solution.