EVIDENCE THAT CERTAIN PHOTOTOXIC DRUGS PHOTOSENSITIZE UROCANIC ACID ISOMERIZATION

Trans to cis photoisomerization of epidermal urocanic acid (UCA) has b een proposed as a primary event in UV-induced immunosuppression. 8-Met hoxypsoralen (8-MOP) in combination with WA radiation (PUVA) is used f or photochemotherapy of several immunoiogically based skin disorders, and PUVA is known to cause immunosuppression. We examined the photoint eraction of 8-MOP and other skin photosensitizing drugs (amiodarone, c iprofloxacin, doxycycline and ketoprofen) with trans-UCA in vitro. In oxic conditions 8-MOP did not enhance the ability of radiation from st andard PUVA fluorescent sources (0.2% radiation below 320 nm) to produ ce cis-UCA, When oxygen was removed, some 8-MOP photosensitization cou ld be detected. 8-MOP, ciprofloxacin and ketoprofen also enhanced inef ficient UCA photoisomerization by radiation from a filtered tungsten h alogen source (0.02% radiation below 320 nm). 8-MOP photosensitization is essential for radiation from PUVA tubes to have a therapeutic or i mmunosuppressive effect. We have shown in vitro that 8-MOP does not en hance cis-UCA production by this source. Extrapolation of our data to the in vivo situation suggests that UCA may not be involved in either the therapeutic or the immunosuppressive effect of PUVA.