van Iperen H P, Brun B M, Caffieri S, Dall'Acqua F, Gasparro F P, Beijersbergen Henegouwen G M
Leiden/Amsterdam Center for Drug Research, Department of Medicinal Photochemistry, State University of Leiden, The Netherlands.
Photochem Photobiol. 1996 May;63(5):577-82. doi: 10.1111/j.1751-1097.1996.tb05659.x.
Photopheresis is an extracorporeal form of photochemotherapy with 8-methoxypsoralen (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 and then reinfused. Photopheresis appears to be effective for several T cell-mediated disorders, because the treatment results in a specific immune response against the pathogenic clone of T cells involved. With PUVA therapy, the whole body of the patient is exposed to UVA, after ingestion of 8-MOP. Upon UVA exposure 8-MOP binds to, amongst others, DNA and induces DNA monoadducts and interstrand cross-links. As a result of these photoadducts photocarcinogenicity is a risk in PUVA. In PUVA 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 photopheresis could also be effective we used, specifically, 4,6,4'-trimethylangelicin (TMA). In this report, we compare the photodegradation of both TMA and 8-MOP under conditions relevant to the in vivo situation, as well as the effect both compounds have on the viability of rat lymphocytes as measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. We show that TMA did not induce immunosuppression in vivo, even after extensive irradiation. In addition a dose dependency of 8-MOP/UVA versus the induced immune suppression was carried out. It was shown that there is a log dose/response correlation of r=0.9205.
光化学疗法是一种使用8-甲氧基补骨脂素（8-MOP）和紫外线A（UVA）的体外光化学疗法（PUVA）。患者口服8-MOP，然后通过离心获得富含补骨脂素的血沉棕黄层，并与盐水混合。该混合物通过UVA辐射场再循环，然后回输。光化学疗法似乎对几种T细胞介导的疾病有效，因为该治疗会引发针对所涉及的致病T细胞克隆的特异性免疫反应。在PUVA疗法中，患者在口服8-MOP后全身暴露于UVA。暴露于UVA后，8-MOP除了与DNA结合外，还会诱导DNA单加合物和链间交联。由于这些光加合物，PUVA存在光致癌风险。在用于治疗银屑病的PUVA中，已证明角型呋喃香豆素虽然几乎不能诱导DNA交联（致癌性较低），但仍然有效。为了确定光化学疗法诱导的单加合物是否也有效，我们特别使用了4,6,4'-三甲基白芷素（TMA）。在本报告中，我们比较了TMA和8-MOP在与体内情况相关的条件下的光降解情况，以及这两种化合物对大鼠淋巴细胞活力的影响（用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法测定）。我们表明，即使经过大量照射，TMA在体内也不会诱导免疫抑制。此外，还进行了8-MOP/UVA与诱导的免疫抑制之间的剂量依赖性研究。结果表明，存在r = 0.9205的对数剂量/反应相关性。
