共查询到20条相似文献,搜索用时 187 毫秒
1.
Syed I. A. Zaidi Rajesh Agarwal Guido Eichler Boris D. Rihter Malcolm E. Kenney Hasan Mukhtar 《Photochemistry and photobiology》1993,58(2):204-210
Abstract— Photodynamic therapy (PDT) of cancer is a modality that relies upon the irradiation of tumors with visible light following selective uptake of a photosensitizer by the tumor tissue. There is considerable emphasis to define new photosensitizers suitable for PDT of cancer. In this study we evaluated six phthalocyanines (Pc) for their photodynamic effects utilizing rat hepatic microsomes and human erythrocyte ghosts as model membrane sources. Of the newly synthesized Pc, two showed significant destruction of cytochrome P-450 and monooxygenase activities, and enhancement of lipid peroxidation, when added to microsomal suspension followed by irradiation with ∼ 675 nm light. These two Pc named SiPc IV (HOSiPcOSi[CH3 ]2 [CH2 ]3 N[CH3 ]2 ) and SiPc V (HOSiPcOSi[CH3 ]2 [CH2 ]3 N[CH3 ]3 1 I) showed dose-dependent photodestruction of cytochrome P-450 and monooxygenase activities in liver microsomes, and photoenhancement of lipid peroxidation, lipid hydroperoxide formation and lipid fluorescence in rnicrosomes and erythrocyte ghosts. Compared to chloroaluminum phthalocyanine tetrasulfonate, SiPc IV and SiPc V produced far more pronounced photodynamic effects. Sodium azide, histidine, and 2,5-dimethylfuran, the quenchers of singlet oxygen, afforded highly significant protection against SiPc IV- and SiPc V-mediated photodynamic effects. However, to a lesser extent, the quenchers of superoxide anion, hydrogen peroxide and hydroxyl radical also showed some protective effects. These results suggest that SiPc IV and SiPc V may be promising photosensitizers for the PDT of cancer. 相似文献
2.
Abstract— Laser flash photolysis of trans -[Rh(dppe)2 X2 ][PF6 ] (X=Br and I; dppe=bis(diphenylphosphino)ethane) in CH2 Cl2 or CH3 CN produces the d7 Rh(II) radicals, [Rh(dppe)2 X]+ , and halogen atoms. The kinetics of the disappearance of [Rh(dppe)2 X]+ radicals in CH2 Cl2 or CH3 CN were mixed order: H-atom abstraction from solvent to produce the rhodium hydrides, [RhH(dppe)2 X][PF6 ], and Rh/X recombination. In the poor H-atom donor solvent, benzonitrile, Rh/Br recombination was observed to be uncomplicated by competing H-atom abstraction. The hydride complexes [RhH(dppe)2 X][PF6 ], formed by H-atom abstraction were completely characterized by 31 P{1 H}-NMR, 1 H-NMR, and mass specrometry. Cyclohexene was used as an effective trap for photogenerated Br atoms and yielded bromocyclohexane and 3-bromocyclohexene in a relative yield, 1:9. The photochemical mechanism is discussed in light of the transient absorbance and trapping studies. 相似文献
3.
B. D. Hirsch N. C. Walz B. E. Meeker M. R. Arnfield J. Tulip M. S. McPhee J. D. Chapman 《Photochemistry and photobiology》1987,46(5):847-852
Abstract The administration of misonidazole (MISO) to Fischer x Copenhagen rats whose R3327-H prostate tumors were treated with photodynamic therapy (PDT) produced enhanced tumor growth delays and cures. This potentiation of PDT by MISO was previously observed with R3327-AT tumors and was postulated to result from drug cytotoxicity of naturally-occurring and PDT-induced hypoxic cells. Radioactively-labelled MISO has been developed as a marker for tissue p02 at the cellular level and [3 H]MISO was administered to R3327-AT and R3327-H tumor-bearing rats before and after standard PDT treatments. The amount of 3 H in tissues 24 h after drug administration was a measure of'bound MISO'which reflects average tissue oxygenation. [3 H]MISO retained in R3327-AT tumors was ˜4x and in liver tissue ˜2x that retained in muscle, heart, brain and R3327-H tumors (1x). Tumors treated with Photofrin II and lased with 1000 J showed a 6-fold increase in retained [3 H]MISO in R3327-H tumors and a 2-fold increase in retained [3 H]MISO in R3327-AT tumors. The absolute levels of retained 3 H in both tumors after PDT were similar. These data provide direct evidence that PDT induces rapid hypoxia in both tumors. When the gastrocnemius muscle of the rat leg was similarly treated, the amount of [3 H]MISO retained was ˜4x greater than that in untreated muscle. This result suggests that PDT-induced hypoxia is not selective to just tumor tissue. These data suggest that the hypoxia-inducing property of PDT might be exploited in combination with hypoxic cell cytotoxins to produce improved tumor responses and cures. 相似文献
4.
James Elver Johnson Mohammad Arfan Richard Hodzi Lyman R. Caswell Susan Rasmussen 《Photochemistry and photobiology》1990,51(2):139-144
Abstract— Photolysis at 254 nm of alkyl benzohydroxamates [C, H, CONHOR: R = CH3 H2 CH3 CH(CH3 )2 , CH2 C6 H5 CH(CH3 )C2 H5 CH(CH3 )- n -C6 H13 ] in acetonitrile or hydrocarbon solvents gives benzamide. These reactions can be sensitized by benzophenone (at ca. 350 nm) and are quenched by cis-piperylene. Racemization occurred when 2-octyl (+)-benzohydroxamate was irradiated in cyclohexane. These results are consistent with a mechanism involving a triplet biradical. Photolysis of phenyl benzohydroxamate [C6 H5 CONHOC6 H5 ] and benzyl N -methylbenzohydroxamate [C6 H5 CON-(CH3 )OCH2 Q6 H5 ] cannot be quenched with ris-piperylene and appear to be singlet reactions. 相似文献
5.
E. Ben-Hur N. E. Geacintov B. Studamire M. E. Kenney B. Horowitz 《Photochemistry and photobiology》1995,61(2):190-195
Abstract— Phthalocyanines are being studied as photosensitizers for virus sterilization of red blood cells (RBC). During optimization of the reaction conditions, we observed a marked effect of the irradiance on production of RBC damage. Using a broad-band light source (600–700 nm) between 5 and 80 mW/ cm2 , there was an inverse relationship between irradiance and rate of photohemolysis. This effect was observed with aluminum sulfonated phthalocyanine (AlPcSn ) and cationic silicon (HOSiPc-OSi[CH3 ]2 [CH2 ]3 N+ [CH3 ]3 I- phthalocyanine (Pc5) photosensitizers. The same effect occurred when the reduction of RBC negative surface charges was used as an endpoint. Under the same treatment conditions, vesicular stomatitis virus inactivation rate was unaffected by changes in the irradiance. Reduction in oxygen availability for the photochemical reaction at high irradiance could explain the effect. However, theoretical estimates suggest that oxygen depletion is minimal under our conditions. In addition, because the rate of photohemolysis at 80 mW/cm2 was not increased when irradiations were carried out under an oxygen atmosphere this seems unlikely. Likewise, formation of singlet oxygen dimoles at high irradiances does not appear to be involved because the effect was unchanged when light exposure was in D2 O. While there is no ready explanation for this irradiance effect, it could be used to increase the safety margin of RBC virucidal treatment by employing exposure at high irradiance, thus minimizing the damage to RBC. 相似文献
6.
Abstract— L5178Y-R (LY-R) and L5178Y-S (LY-S) cells differ in sensitivity to UVC radiation (D0 : 2.8 and 9.0 J/m2 respectively, for cells exposed in Fischer's medium). We used these cells and a DNA unwinding technique in conjunction with 1-β-D-arabinosyl cytosine to determine DNA strand breaks accumulating as a result of enzymatic incision during DNA repair. Following UVC exposure DNA strand break accumulation was observed in LY-S cells but not in LY-R cells. The repair defect in LY-R cells is accompanied by a delayed recovery of [3 H]thymidine incorporation. 相似文献
7.
Paul Gottlieb Li-Gang Shen Eleanor Chimezie Soon Bahng Malcolm E. Kenney Bernard Horowitz Ehud Ben-Hur 《Photochemistry and photobiology》1995,62(5):869-874
Abstract— -Three phthalocyanine dyes HOSiPcOSi(CH3 )2 (CH2 )3 N(CH3 )2 (Pc 4), HOSiPc-OSi(CH3 )2 (CH2 )3 N+(CH3 )3I- (Pc 5) and aluminum tetrasulfophthalocyanine hydroxide (AlOHPcS4 ) were evaluated for their ability to inactivate the trypomastigote form of Trypanosoma cruzi in fresh frozen plasma (FFP) and red blood cell concentrates (RBCC). The compound Pc 4 was found to be highly effective in killing T. cruzi, Pc 5 less effective and AlOHPcS4 ineffective. With FFP as the medium, a complete loss of parasite infectivity in vitro (≥5 log10 ) was found to occur with 2 μ M Pc 4 after irradiation with red light (>600 nm) at a fiuence of 7.5 J/cm2 , while with RBCC as the medium, a complete loss was found to occur at a fiuence of 15 J/cm2 . Even without illumination, Pc 4 at 2 μ M also killed about 3.7-4.1 log10 of T. cruzi in FFP during 30 min. Observed differences in T. cruzi killing by the various phthalocyanines may relate to differences in binding; Pc 4 binds to the parasites about twice as much as Pc 5. Ultrastructural analysis of treated parasites suggests that mitochondria are a primary target of this photodynamic treatment. The data indicate that Pc 4 combined with exposure to red light could be used to eliminate bloodborne T. cruzi parasites from blood components intended for transfusion. The inactivation of T. cruzi by Pc 4 in the dark suggests a possible therapeutic application. 相似文献
8.
Abstract— The ability of photodynamic treatment (PDT) with the phthalocyanine Pc 4 to activate cellular signal transduction pathways in murine lymphoma L5178Y-R cells has been assessed by observing increases in protein tyrosine phosphorylation at early times post-PDT. Western blot analysis with an anti-phosphotyrosine antibody revealed a dramatic increase in phosphorylation of two major protein bands of Mr -80000 and -55000 in response to PDT. The increase was PDT dose-dependent, occurred as early as 20 s after initiation of light exposure of Pc 4-pre-loaded cells and was amplified by the presence of the protein tyrosine phosphatase inhibitor, sodium ortho-vanadate (NaV04 ). By immunoprecipitation, one of the Mr –80000 phosphorylated proteins has been identified as HS1, a substrate of nonreceptor-type protein tyrosine kinases. Although vanadate greatly enhanced the level and extent of PDT-induced phosphorylation, it had no influence on overall photocytotoxicity or on the rate of apoptotic DNA fragmentation. Genistein, an inhibitor of protein tyrosine kinases, diminished tyrosine phosphorylation of the Mr –80000 and other proteins and dramatically potentiated cell killing induced by PDT but did not significantly affect PDT-induced apoptosis. The results suggest that PDT rapidly activates a membrane-associated src family kinase(s) in L5178Y-R cells, one substrate of which is HS1, and that protein tyrosine phosphorylation is part of a stress response, protecting a portion of the cells from the lethal effects of PDT but not altering the mechanism by which they die. 相似文献
9.
Michael Price Stanley R. Terlecky David Kessel 《Photochemistry and photobiology》2009,85(6):1491-1496
Although the first reactive oxygen species (ROS) formed during irradiation of photosensitized cells is almost invariably singlet molecular oxygen (1 O2 ), other ROS have been implicated in the phototoxic effects of photodynamic therapy (PDT). Among these are superoxide anion radical (• O2 − ), hydrogen peroxide (H2 O2 ) and hydroxyl radical (• OH). In this study, we investigated the role of H2 O2 in the pro-apoptotic response to PDT in murine leukemia P388 cells. A primary route for detoxification of cellular H2 O2 involves the peroxisomal enzyme catalase. Inhibition of catalase activity by 3-amino-1,2,4-triazole led to an increased apoptotic response. PDT-induced apoptosis was impaired by addition of an exogenous recombinant catalase analog (CAT- skl) that was specifically designed to enter cells and more efficiently localize in peroxisomes. A similar effect was observed upon addition of 2,2'-bipyridine, a reagent that can chelate Fe+2 , a co-factor in the Fenton reaction that results in the conversion of H2 O2 to • OH. These results provide evidence that formation of H2 O2 during irradiation of photosensitized cells contributes to PDT efficacy. 相似文献
10.
L. S. Lussier C. Sandorfy H. OA L E-Thanh D. Vocelle 《Photochemistry and photobiology》1987,45(S1):801-808
Abstract— The Fourier-transform infrared spectra of chloroform-d solutions of conjugated imines CH3 CH=CHCH=NCH(CH3 )2 and CH3 CH2 CH=CHCH=CHCH=NCH(CH3 )2 and the related protonated species with HCl, HBr, HI, trichloro, dichloro, monobromo and monochloroacetic acids or propionic acid are presented. The effects of conjugation and protonation are examined. The results show that conjugation slightly increases the basicity of the Schiff bases. HCl, HBr and HI protonate the Schiff bases completely. The carboxylic acids protonate partially depending on their p K a , values. When the Schiff base contains two (or more) C=C bonds conjugated with C=N, the main C=C stretching band undergoes a strong intensification showing that sizeable dipole moment variations occur along the conjugated chain. 相似文献
11.
Rapid Initiation of Apoptosis by Photodynamic Therapy 总被引:6,自引:1,他引:6
Abstract— Photodynamic therapy (PDT) of neoplastic cell lines is sometimes associated with the rapid initiation of apoptosis, a mode of cell death that results in a distinct pattern of cellular and DNA fragmentation. The apoptotic response appears to be a function of both the sensitizer and the cell line. In this study, we examined photodynamic effects of several photosensitizers on murine leukemia P388 cells. Two drugs, a porphycene dimer (PcD) and tin etiopurpurin (SnET2), which localized at lysosomal sites, were tested at PDT doses that resulted in 50% loss of viability (LD50 ), measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. An oligonucleosomal pattern of DNA degradation was observed within 1 h after irradiation. Neither sensitizer antagonized PDT-mediated internucleosomal DNA cleavage by the other. Very high PDT doses with either agent abolished this rapid internucleosomal cleavage. Exposure of cells to high concentrations of either sensitizer in the dark also resulted in rapid DNA fragmentation to nucle-osomes and nucleosome multimers; this effect was not altered by the antioxidant 6-hydroxy-2,5,7,8-tetramethyl-chroman-2-carboxylic acid (trolox), although the latter could protect cells from cytotoxicity and apoptotic effects caused by LD50 PDT doses. Photodamage from two cat-ionic sensitizers, which localized at membrane sites, caused rapid DNA cleavage to 50 kb particles; however, no further fragmentation was detected after 1 h under LD10 , LD50 or LD95 PDT conditions. Moreover, the presence of either cationic sensitizer inhibited the rapid internucleosomal cleavage induced by SnET2 or PcD photodamage. The site of photodynamic action may therefore be a major determinant of the initiation and rate of progression of apoptosis. 相似文献
12.
Abstract— Polymer rose bengal derivatives are converted to their C-6 ammonium salts. The φ1 O2 derived in CH2 C12 is a function of the K B of the neutralizing amine. 相似文献
13.
Paul A. J. Link Henk C. VAN DER Plas Franz Müller 《Photochemistry and photobiology》1987,45(5):557-563
Abstract— Absorption, fluorescence and phosphorescence spectra as well as fluorescence and phosphorescence quantum yields of 8-X-5-deazaflavins (X = C1, NO2 , p -NO2 -C6 H4 , N(CH3 )2 , NH2 , p -NH2 -C6 H4 , p -N(CH3 )2 -C6 H4 -N=N) were determined. It was found that all these data are highly influenced by the substituent at position 8 of the 5-deazaisoalloxazine skeleton. Also the photoreduction of 8-X-5-deazaflavins in the presence of electron donors was studied. It was established that the photoreduction leads to the formation of a 5,5'-dimer and/or a 6,7-dihydro compound. Reduction of the C(6)-C(7) bond is promoted by strong electron-donating substituents and bulky electron donors. 5-Deazaftavins with a reducible substituent at position 8 exhibit reduction of the substituent prior to the reduction of the 5-deazaisoalloxazine skeleton. 相似文献
14.
A Water-Soluble Luminescence Oxygen Sensor 总被引:1,自引:0,他引:1
We developed a water-soluble luminescent probe for dissolved oxygen. This probe is based on (Ru[dpp(SO3 Na)2 ]3 ) Cl2 , which is a sulfonated analogue of the well-known oxygen probe (Ru[dpp]3 )Cl2 . The compound dpp is 4,7-diphenyl-1,10-phenanthroline and dpp(SO3 Na)2 is a disulfonated derivative of the same ligand. In aqueous solution in the absence of oxygen (Ru[dpp(SO3 Na)2 ]3 )Cl2 displays a lifetime of 3.7 μs that decreases to 930 ns on equilibrium with air and 227 ns on equilibrium with 100% oxygen. The Stern–Vohner quenching constant is 11330 M−1 . This high oxygen-quenching constant means that the photoluminescence of Ru(dpp[SO3 Na]2 )3 Cl2 is 10% quenched at an oxygen concentration of 8.8 x 10−6 M , or equilibration with 5.4 torr of oxygen. The oxygen probe dissolved in water displays minimal interactions with lipid vesicles composed of dipalmityl-L-α-phosphatidyl glycerol but does appear to interact with human serum albumin. The absorption maximum near 480 nm, long lifetime and large Stokes'shift allow this probe to be used with simple instrumentation based on a light-emitting diode light source, allowing low-cost oxygen sensing in aqueous solutions. To the best of our knowledge this is the first practical water-soluble oxygen sensor. 相似文献
15.
P. F. HEELIS B. J. PARSONS G. O. PHILLIPS A. J. SWALLOW 《Photochemistry and photobiology》1991,53(1):21-23
Abstract— The one-electron reduction and oxidation of 5,10-methenyltetrahydrofolate has been studied in aqueous solution in the acidity range H0 = -1 to pH = 7 using the reducing species CO- 2 and (CH3 )2 -COH and oxidising species Br- 2 , and H2 SeO+3 . The spectral and other properties of the radicals so formed were found to be indcpendent of the reductant/oxidant used. Two protolytic forms of both the oxidised and reduced radicals were observed with approximate p K , values of 0.5 ± 0.3 being determined. Both the bridged form (5.10-methenyltetrahydrofolate) and the unbridged form (5- formyltetrahydrofolate) were found to be easily oxidised, whereas only the former could be reduced. 相似文献
16.
Gurmit Singh Brian C. Wilson Sheila M. Sharkey George P. Browman Paula Deschamps 《Photochemistry and photobiology》1991,54(2):307-312
A degree of resistance to photodynamic therapy (PDT) has been induced in radiation-induced fibrosarcoma-1 (RIF-1) tumor cells by repeated photodynamic treatment with Photofrin (4 or 18 h incubation) in vitro to the 0.1-1% survival level, followed by regrowth from single surviving colonies. The resistance is shown as increased cell survival in the strain designated RIF-8A, compared to the wild-type RIF-1 cells, when exposed to increasing Photofrin concentration for 18 h incubation and fixed light exposure. No difference was found between RIF-1 and RIF-8A in the uptake of Photofrin per unit cell volume at 18 h incubation. Resistance to PDT was also observed in Chinese hamster ovary-multi-drug resistant (CHO-MDR) cells compared to the wild-type CHO cells, possibly associated with decreased cellular concentration of Photofrin in the former. By contrast, the PDT-resistant RIF-8A cells did not show any cross-resistance to Adriamycin, nor was there any significant drug concentration difference between RIF-1 and RIF-8A. These findings suggest that different mechanisms are responsible for PDT-induced resistance and multi-drug resistance. 相似文献
17.
Eberhard Bothe Man Nien Schuchmann Dietrich Schulte-Frohlinde Clemens von Sonntag 《Photochemistry and photobiology》1978,28(4-5):639-643
Abstract— In aqueous solutions α-hydroxyalkylperoxyl radicals undergo a spontaneous and a base catalysed HO2 elimination. From kinetic deuterium isotope effects, temperature dependence, and the influence of solvent polarity it was concluded that the spontaneous reaction occurs via an HO2 elimination followed by the dissociation of the latter into H+ and O2 - . The rate constant of the spontaneous HO2 elimination increases with increasing methyl substitution in α-position ( k (CH2 (OH)O2 ) < 10s-1 k (CH3 CH(OH)O2 ) = 52s-1 k ((CH3 )2 C(OH)O2 ) = 665 s-1 ). The OH- catalysed reaction is somewhat below diffusion controlled. The mixture of peroxyl radicals derived from polyhydric alcohols eliminate HO2 at two different rates. Possible reasons for this behaviour are discussed. The mixture of the six peroxyl radicals derived from d -glucose are observed to eliminate HO2 with at least three different rates. The fastest rate is attributed to the HO2 elimination from the peroxyl radical at C-l ( k > 7000s-1 ). Because of the HO2 eliminations the peroxyl radicals derived from d -glucose do not undergo a chain reaction in contrast to peroxyl radicals not containing an α-OH group. In competition with the first order elimination reactions the α-hydroxylalkylperoxyl radicals undergo a bimolecular decay. These reactions are briefly discussed. 相似文献
18.
Makito Miyake Masazumi Ishii Kiyotaka Kawashima Tetsuro Kodama Kokichi Sugano Kiyohide Fujimoto Yoshihiko Hirao 《Photochemistry and photobiology》2009,85(4):1020-1027
Photodynamic therapy mediated by 5-aminolevulinic acid (ALA-PDT) has been developed as a therapeutic modality for refractory superficial bladder cancers. Here, in experiments using urothelial cancer cell lines, we investigated the effects of siRNA modulating heme-synthetic and degradation pathways for ALA-PDT. Targeted knockdown of ferrochelatase (FECH) suppressed heme synthesis and significantly increased intracellular protoporphyrin IX (PpIX) accumulation, leading to enhanced phototoxicity in four of five cell lines. Heme oxygenase-1 (HO-1) is recognized as important for cytoprotection against oxidative stress such as PDT. Targeted knockdown of HO-1 leads to decreased intracellular PpIX accumulation, resulting in a failure to enhance ALA-PDT effect in four cell lines. Knockdown of HO-1 caused marked growth inhibition in UM-UC-2 overexpressing HO-1, whereas no inhibitory effect was observed in UM-UC-3 lacking HO-1 expression. Moreover, HO-1 protein levels and (GT) n repeat polymorphism of the HO-1 gene promoter region were examined with the implication that the constitutive expressions of HO-1 protein were associated with a shorter (GT) n repeat. Our results suggested that (1) FECH siRNA improved the phototoxicity of ALA-PDT, (2) overexpression of HO-1 was associated with shorter (GT) n repeat of the promoter region, and (3) siRNA-mediated knockdown of HO-1 could suppress the growth of bladder cancer cells overexpressing HO-1. 相似文献
19.
Abstract. The data of Kung and DeVault (1978) showing high-order fluorescence from chromatophores of photosynthetic bacteria are analyzed in relation to other data on first-order fluorescence of photosynthetic systems, particularly that of Monger and Parson (1977). The wavelengths of emission observed (down to 445 nm) require energy equivalent to two lowest singlet-excited states. The dependence on excitation intensity is best explained by any of the following third-order processes: (a) 3 S 1 →3 S 0 ; (b) 2 S 1 + T , → 2 S 0 + T 1 ; (c) S 1 + 2 T 1 → 3 S 0 . However, (c) is ruled out because it predicts heavy T 1 -destruction which is not observed. Contribution from the second order process: 2 S 1 → S 0 is probable, but even the data of Monger and Parson show that it is insufficient by itself. Two-photon absorption: S 0 + hv 1 → S 1 ; S 1 + hv 1 → S n ; S n S 0 + hv 2 could also account for the high-order fluorescence and its dependence on excitation intensity. [ S 0 , S 1 S n are ground, first excited and a higher excited singlet states, respectively, of antenna bacteriochlorophyll, T t is the lowest triplet state, c/v , is the exciting wavelength (694 or 868 nm) and c/v 2 the wavelength of the high-order fluorescence (445, 535. or 600 nm), where c = velocity of light.] Maximum values are estimated for some of the rate constants. 相似文献
20.
Saeko Tada-Oikawa Shinji Oikawa Junya Hirayama Kazutaka Hirakawa Shosuke Kawanishi 《Photochemistry and photobiology》2009,85(6):1391-1399
Cancer photodynamic therapy (PDT) requires photosensitizers that efficiently and selectively destroy tumor cells. We investigated 5,10,15,20-tetrakis ( N -methyl-4-pyridyl)-21 H ,23 H -porphyrin (TMPyP) as a potential cancer treatment. Confocal fluorescence microscopy showed that TMPyP was localized in the nuclei, whereas 5-aminolevulinic acid (ALA)-derived protoporphyrin IX (PPIX) was localized diffusely in the cytoplasm of human leukemia (HL-60) cells. In HL-60 cells under UVA irradiation, TMPyP effectively induced apoptosis. Moreover, 8-oxo-7,8-dihydro-2'-deoxyguanosine, an oxidative product of 2'-deoxyguanosine, was accumulated in the DNA of cells treated with photoirradiated TMPyP, whereas only small amounts were observed in ALA-treated cells in the presence of UVA light. TMPyP and UVA caused extensive damage at every guanine residue in DNA fragments obtained from the human p 53 tumor suppressor gene and the c-Ha- ras -1 proto-oncogene, whereas PPIX induced little DNA damage under these conditions. Electron spin resonance spectroscopy using a singlet oxygen (1 O2 ) probe and D2 O showed that photoexcited TMPyP generated 1 O2 . These results suggest that photoexcited TMPyP reacts with oxygen to generate 1 O2 , which in turn, oxidizes guanine residues. Taken together, the results demonstrated that TMPyP was localized in the nucleus where it was photosensitized to induce DNA damage, suggesting that TMPyP may have clinical utility as a nucleus-targeted PDT. 相似文献