THE LACK OF EFFICACY OF 4,6,4'-TRIMETHYLANGELICIN TO INDUCE IMMUNE SUPPRESSION IN AN ANIMAL-MODEL FOR PHOTOPHERESIS - A COMPARISON WITH 8-MOP

Photopheresis is an extracorporeal form of photochemotherapy with 8-me thoxypsoralen (8-MOP) and UVA (PUVA). Patients ingest 8-MOP and then a psoralen-rich buffy coat is obtained by centrifugation and mixed with saline. This mixture Is recirculated through a UVA radiation field an d then reinfused. Photopheresis appears to be effective for several T cell-mediated disorders, because the treatment results in a specific i mmune response against the pathogenic clone of T cells involved. With PUVA therapy, the whole body of the patient is exposed to UVA, after i ngestion of 8-MOP. Upon UVA exposure 8-MOP binds to, amongst others, D NA and induces DNA monoadducts and interstrand cross-links. As a resul t of these photoadducts photocarcinogenicity is a risk in PUVA. In PUV A for psoriasis, it proved that angular furocoumarins, although almost incapable of inducing DNA cross-links (less carcinogenic), are still effective. In order to determine if monoadducts induced by photopheres is could also be effective we used, specifically, 4,6,4'-trimethylange licin (TMA). In this report, we compare the photodegradation of both T MA and 8-MOP under conditions relevant to the in vivo situation, as we ll as the effect both compounds have on the viability of rat lymphocyt es as measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetr azolium bromide (MTT) assay. We show that TMA did not induce immunosup pression in vivo, even after extensive irradiation. In addition a dose dependency of 8-MOP/UVA versus the induced immune suppression was car ried out. It was shown that there is a log dose/response correlation o f r = 0.9205.