Photochemical and photobiological studies of a furonaphthopyranone as a benzo-spaced psoralen analog in cell-tree and cellular DNA

被引:8
作者
Adam, W
Mielke, K
SahaMoller, CR
Moller, M
Stopper, H
Hutterer, R
Schneider, FW
Ballmaier, D
Epe, B
Gasparro, FF
Cheng, XS
Kagan, J
机构
[1] UNIV WURZBURG, DEPT TOXICOL, D-97074 WURZBURG, GERMANY
[2] UNIV WURZBURG, INST PHYS CHEM, D-97074 WURZBURG, GERMANY
[3] UNIV MAINZ, INST PHARM, D-6500 MAINZ, GERMANY
[4] THOMAS JEFFERSON UNIV, DEPT DERMATOL & CUTANEOUS BIOL, PHILADELPHIA, PA USA
[5] UNIV ILLINOIS, DEPT CHEM, CHICAGO, IL 60680 USA
关键词
D O I
10.1111/j.1751-1097.1997.tb03137.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 glycosylase (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 D2O 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 (Delta G(ET) ca -5 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.
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页码:46 / 54
页数:9
相关论文
共 60 条
[1]   COMPARISON OF THE AS52/XPRT AND THE CHO/HPRT ASSAYS - EVALUATION OF 6 DRUG CANDIDATES [J].
AARON, CS ;
STANKOWSKI, LF .
MUTATION RESEARCH, 1989, 223 (02) :121-128
[2]   SYNTHESIS AND PHOTOOXYGENATION OF THE 2H-4,8,9-TRIMETHYLFURO[2',3'/5,6]NAPHTHO[1,2-B]-PYRAN-2-ONE, AND UNNATURAL FUROCOUMARIN WITH A BENZENE SPACER [J].
ADAM, W ;
QIAN, XH ;
SAHAMOLLER, CR .
JOURNAL OF ORGANIC CHEMISTRY, 1993, 58 (14) :3769-3771
[3]   NEW ASPECTS OF THE REPAIR AND GENOTOXICITY OF PSORALEN PHOTOINDUCED LESIONS IN DNA [J].
AVERBECK, D ;
DARDALHON, M ;
MAGANASCHWENCKE, N ;
MEIRA, LB ;
MENIEL, V ;
BOITEUX, S ;
SAGE, E .
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 1992, 14 (1-2) :47-63
[4]   EFFECT OF MOLECULAR-STRUCTURE ON THE PHOTOPHYSICAL PROPERTIES, THE PHOTOREACTIVITY WITH DNA AND THE PHOTOBIOLOGICAL ACTIVITY OF MONOFUNCTIONAL PYRIDOPSORALENS [J].
BLAIS, J ;
AVERBECK, D ;
MORON, J ;
BISAGNI, E ;
VIGNY, P .
PHOTOCHEMISTRY AND PHOTOBIOLOGY, 1987, 45 (04) :465-472
[5]   PROPERTIES AND BIOLOGICAL FUNCTIONS OF THE NTH AND FPG PROTEINS OF ESCHERICHIA-COLI - 2 DNA GLYCOSYLASES THAT REPAIR OXIDATIVE DAMAGE IN DNA [J].
BOITEUX, S .
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 1993, 19 (02) :87-96
[6]  
BOITEUX S, 1990, J BIOL CHEM, V265, P3916
[7]  
BORDIN F, 1994, TRENDS PHOTOCHEMISTR, V3, P343
[8]   THYMINE LESIONS PRODUCED BY IONIZING-RADIATION IN DOUBLE-STRANDED DNA [J].
BREIMER, LH ;
LINDAHL, T .
BIOCHEMISTRY, 1985, 24 (15) :4018-4022
[9]   ISOLATION AND CHARACTERIZATION OF A NEW PRODUCT PRODUCED BY IONIZING IRRADIATION AND TYPE-I PHOTOSENSITIZATION OF 2'-DEOXYGUANOSINE IN OXYGEN-SATURATED AQUEOUS-SOLUTION - (2S)-2,5'-ANHYDRO-1-(2'-DEOXY-BETA-D-ERYTHRO-PENTOFURANOSYL)-5-GUANIDINYLIDENE-2-HYDROXY-4-OXOIMIDAZOLIDINE [J].
BUCHKO, GW ;
CADET, J ;
RAVANAT, JL ;
LABATAILLE, P .
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1993, 63 (06) :669-676
[10]  
CADET J, 1983, ISRAEL J CHEM, V23, P420