Photochemotherapy (PUVA) of psoriasis using 3-carbethoxypsoralen, a non-carcinogenic compound in mice

Abstract

The carcinogenic risk of photochemotherapy (PUVA) with bi‐functional furocoumarins such as 8‐methoxypsoralen (8‐MOP) which form cross‐links in cellular DNA has initiated a search for active but less hazardous psoralens. A new compound, 3‐carbethoxypsoralen (3‐CPs), studied in the yeast Saccharomyces cerevisiae (eukaryote), has been shown to be very photoactive on DNA and to form only mono‐additions to DNA. These lesions appear to be more easily repaired than the cross‐links induced by 8‐MOP. 3‐CPs produces less nuclear genetic events such as nuclear mutations and mitotic crossovers, but more cytoplasmic ‘petite’ mutations (damage to mitochondrial DNA) than 8‐MOP. In mice it was demonstrated that after local or intra‐peritoneal administration, in contrast to 8‐MOP. 3‐CPs is non‐toxic, non‐erythematogenic, and non‐carcinogenic. A study of ten psoriatic patients has shown that local applications of 3‐CPs plus UV‐A exhibit about the same therapeutic activity for the clearing of psoriatic lesions as local treatment with 8‐MOP plus UV‐A, but without any localized hyperpigmentation.