Photophysical and photobiological properties of 3-carbethoxypsoralen.
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.
Joshi
P C
PC
Department of Dermatology, Harvard Medical School, Massachusetts General Hospital, Boston 02114, USA.
Pathak
M A
MA
D000818:Animals; D011564:Furocoumarins / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D014466:Ultraviolet Rays
D011564:Furocoumarins; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; C017104:3-carbethoxypsoralen