Joshi P C, Pathak M A
Department of Dermatology, Harvard Medical School, Massachusetts General Hospital, Boston 02114, USA.
Indian J Biochem Biophys. 1995 Apr;32(2):63-73.
3-Carbethoxypsoralen (3-CP), a linear tricyclic psoralen, known for its photoreaction with DNA to form monofunctional cyclobutane adducts with pyrimidine bases, was found to produce a highly reactive cytotoxic species, singlet oxygen (1O2) to a greater extent than several other linear psoralens such as psoralen, 8-MOP, 5-MOP or angular psoralens (angelicin). 3-CP also produced superoxide radicals (O2-.) at a rate slower than psoralens in the following order:psoralen > angelicin > 3-CP > 8-MOP > 5-MOP. 1O2 produced by photoactivated 3-CP was found to oxidize tyrosine and Dopa to Dopachrome, and subsequently their conversion to melanin. It also induced photooxidation of 2'-deoxyguanosine. Reactive oxygen species produced by 3-CP also induced lipid peroxidation. The rate of dopachrome formation to promote its conversion to melanin and lipid peroxidation by 3-CP and other linear and angular psoralens and hematoporphyrin derivatives may be related to their skin photosensitizing ability and the rate of 1O2 production. Topically applied 3-CP on hairless mice exposed to UVA radiation was found to be a nonphotocarcinogenic agent in contrast to 8-MOP, which under similar conditions produced a 70% tumour yield (squamous cell carcinoma) in 65 weeks. 3-CP was observed to be a photolabile compound and was converted to a dihydro-form as previously reported by other investigators. The photoconversion of 3-CP to 4',5'-dihydro-3-CP was enhanced under N2, whereas, under O2 atmosphere, lesser degree of photoconversion was observed, thus, indicating that reduction takes place via an anoxic or Type I mechanism. The significance of these observations are discussed in relation to the skin photosensitizing, nonphotocarcinogenic, and photochemotherapeutic potential of 3-CP.
3-乙氧羰基补骨脂素（3-CP）是一种线性三环补骨脂素，以其与DNA发生光反应形成与嘧啶碱基的单功能环丁烷加合物而闻名，已发现它比其他几种线性补骨脂素（如补骨脂素、8-甲氧基补骨脂素、5-甲氧基补骨脂素）或角型补骨脂素（当归素）能更大程度地产生高反应性细胞毒性物质单线态氧（1O2）。3-CP产生超氧自由基（O2-.）的速率也比补骨脂素慢，顺序如下：补骨脂素＞当归素＞3-CP＞8-甲氧基补骨脂素＞5-甲氧基补骨脂素。发现光活化的3-CP产生的1O2能将酪氨酸和多巴氧化为多巴色素，随后它们转化为黑色素。它还诱导2'-脱氧鸟苷的光氧化。3-CP产生的活性氧也诱导脂质过氧化。3-CP以及其他线性和角型补骨脂素与血卟啉衍生物促进多巴色素形成以转化为黑色素和脂质过氧化的速率可能与其皮肤光敏能力和1O2产生速率有关。与8-甲氧基补骨脂素相比，在无毛小鼠局部涂抹3-CP并暴露于UVA辐射下，发现它是一种非光致癌剂，而8-甲氧基补骨脂素在类似条件下65周内产生了70%的肿瘤发生率（鳞状细胞癌）。观察到3-CP是一种光不稳定化合物，如先前其他研究者所报道的那样会转化为二氢形式。3-CP向4',5'-二氢-3-CP的光转化在氮气下增强，而在氧气气氛下观察到的光转化程度较小，因此表明还原是通过缺氧或I型机制发生的。结合3-CP的皮肤光敏、非光致癌和光化学治疗潜力对这些观察结果的意义进行了讨论。
