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Photochemical and Photobiological Studies of a Furonaphthopyranone as a Benzo‐spaced Psoralen Analog in Cell‐free and Cellular DNA
Author(s) -
Adam Waldemar,
Mielke Karsten,
SahaMöller Chantu R.,
Möller Marianne,
Stopper Helga,
Hutterer Rudolf,
Schneider Friedemann W.,
Ballmaier Daniel,
Epe Bernd,
Gasparro Francis F.,
Chen Xinsheng,
Kagan Jacques
Publication year - 1997
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1997.tb03137.x
Subject(s) - furocoumarin , psoralen , chemistry , dna , dna damage , photochemistry , singlet oxygen , comet assay , oxazolone , biophysics , biochemistry , biology , oxygen , organic chemistry
— Photobiological activities of the benzo‐spaced psoralen analog furonaphthopyranone 3 have been investigated in cell‐free and cellular DNA. The molecular geometry parameters of 3 suggest that it should not form interstrand crosslinks with DNA. With cell‐free DNA no evidence for crosslinking but also not for monoadduct formation was obtained; rather, the unnatural furocoumarin 3 induces oxidative DNA modifications under near‐UVA irradiation. The enzymatic assay of the photosensitized damage in cell‐free PM2 DNA revealed the significant formation of lesions sensitive to formamidopyrimidine DNA glyco‐sylase (Fpg protein). In the photooxidation of calf thymus DNA by the furonaphthopyranone 3, 0.29±0.02% 8‐oxo‐7,8‐dihydroguanine (8‐oxoGua) was observed. With 2′‐deoxyguanosine (dGuo), the guanidine‐releasing photooxidation products oxazolone and oxoimidazolidine were formed predominately, while 8‐oxodGuo and 4‐HO‐8‐oxodGuo were obtained in minor amounts. The lack of a significant D 2 O effect in the photooxidation of DNA and dGuo reveals that singlet oxygen (type II process) plays a minor role; control experiments with tert ‐butanol and mannitol confirm the absence of hydroxyl radicals as oxidizing species. The furonaphthopyranone 3 (E red = ‐1.93±0.03V) should act in its singlet‐excited state as electron acceptor for the photooxidation of dGuo (δG ET ca – kcal/mol), which corroborates photoinduced electron transfer (type I) as a major DNA‐oxidizing mechanism. A comet assay in Chinese hamster ovary (CHO) AS52 cells demonstrated that the psoralen analog 3 damages cellular DNA upon near‐UVA irradiation; however, no photosensitized mutagenicity was observed in CHO AS52 cell cultures