Singlet Oxygen Generation by UVA Light Exposure of Endogenous Photosensitizers

Baier, Johannes; Maisch, Tim; Maier, Max; Engel, Eva; Landthaler, Míchael; Bäumler, Wolfgang

doi:10.1529/biophysj.106.082388

Cited by 295 publications

(239 citation statements)

References 39 publications

Supporting

Mentioning

222

Contrasting

Unclassified

Order By: Relevance

“…However, in combination with UVA1 irradiation, riboflavin treatment could significantly impair cellular viability. It has been shown that UVA irradiation of riboflavin generates reactive intermediate species, such as singlet oxygen, superoxide anions, triplet state riboflavin radicals, and hydrogen peroxide (33)(34)(35). High-dose UVA irradiation alone has also been proven to produce reactive oxygen species with known cytotoxic properties (36).…”

Section: Discussionmentioning

confidence: 99%

Riboflavin activated by ultraviolet A1 irradiation induces oxidative DNA damage-mediated mutations inhibited by vitamin C

Besaratinia

Kim

Bates

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

100

View full text Add to dashboard Cite

An increasingly popular theory ascribes UVA (>320 -400 nm) carcinogenicity to the ability of this wavelength to trigger intracellular photosensitization reactions, thereby giving rise to promutagenic oxidative DNA damage. We have tested this theory both at the genomic and nucleotide resolution level in mouse embryonic fibroblasts carrying the lambda phage cII transgene. We have also tested the hypothesis that inclusion of a cellular photosensitizer (riboflavin) can intensify UVA-induced DNA damage and mutagenesis, whereas addition of an antioxidant (vitamin C) can counteract the induced effects. Cleavage assays with formamidopyrimidine DNA glycosylase (Fpg) coupled to alkaline gel electrophoresis and ligation-mediated PCR (LM-PCR) showed that riboflavin treatment (1 M) combined with UVA1 (340 -400 nm) irradiation (7.68 J/cm 2 ) or higher dose UVA1 irradiation alone induced Fpg-sensitive sites (indicative of oxidized and/or ring-opened purines) in the overall genome and in the cII transgene, respectively. Also, the combined treatment with riboflavin and UVA1 irradiation gave rise to single-strand DNA breaks in the genome and in the cII transgene determined by terminal transferasedependent PCR (TD-PCR). A cotreatment with vitamin C (1 mM) efficiently inhibited the formation of the induced lesions. Mutagenicity analysis showed that riboflavin treatment combined with UVA1 irradiation or high-dose UVA1 irradiation alone significantly increased the relative frequency of cII mutants, both mutation spectra exhibiting significant increases in the relative frequency of G:C 3 T:A transversions, the signature mutations of oxidative DNA damage. The induction of cII mutant frequency was effectively reduced consequent to a cotreatment with vitamin C. Our findings support the notion that UVA-induced photosensitization reactions are responsible for oxidative DNA damage leading to mutagenesis. ultraviolet A radiation ͉ photosensitizer ͉ antioxidant ͉ skin cancer A large body of evidence exists regarding the association between solar UV irradiation and human skin carcinogenesis (1, 2). Sunlight UV wavelengths that reach the surface of the earth are UVA (Ͼ320-400 nm) and UVB (280-320 nm), with shorter wavelengths (UVC) being completely absorbed by stratospheric oxygen (O 2 ) (1, 3). The biologically relevant UVA and UVB have been extensively studied as the etiologic factors for skin cancer (4). The mechanistic involvement of UVB in carcinogenesis rests upon the ability of this wavelength to induce promutagenic cis-syn cyclobutane pyrimidine dimers (CPDs), pyrimidine (6-4) pyrimidone photoproducts ((6-4)PPs), and Dewar valence photoisomers (4). However, the underlying mechanism of action for UVA carcinogenicity is not fully delineated (4). Despite the weak absorbance of UVA by DNA (3), a genotoxic mode of action for UVA has been demonstrated (1). Yet, the exact process through which UVA exerts genotoxicity remains elusive (4).A widely recognized theory ascribes UVA genotoxicity to its ability to trigger intracellular photosensitizat...

show abstract

Section: Discussionmentioning

confidence: 99%

Riboflavin activated by ultraviolet A1 irradiation induces oxidative DNA damage-mediated mutations inhibited by vitamin C

Besaratinia

Kim

Bates

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

100

View full text Add to dashboard Cite

show abstract

“…Specifically, the decay time of the singlet oxygen luminescence signal increased up to 40 s at the highest protein concentration. Thus, it can be stated that (i) the generation of singlet oxygen requires sufficient oxygen concentration (19), and (ii) singlet oxygen can diffuse through different environments, such as bacteria and water.…”

Section: Singlet Oxygen Luminescence For Variable and High Bacterial mentioning

confidence: 99%

“…Recently, a model was developed to estimate the singlet oxygen dose by characterization of Photofrin (Axcan Pharma, Birmingham, AL) photobleaching during photodynamic therapy of eukaryotic cells in vitro (18). Moreover, singlet oxygen can be visualized by measuring its luminescence at 1,270 nm directly in solvents (19,20), in eukaryotic cells (21,22), and even in human skin (23). This time-resolved decay of the luminescence should provide an indication of the site of singlet oxygen in bacteria.…”

mentioning

confidence: 99%

The role of singlet oxygen and oxygen concentration in photodynamic inactivation of bacteria

Maisch¹,

Baier²,

Franz³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

375

289

View full text Add to dashboard Cite

New antibacterial strategies are required in view of the increasing resistance of bacteria to antibiotics. One promising technique involves the photodynamic inactivation of bacteria. Upon exposure to light, a photosensitizer in bacteria can generate singlet oxygen, which oxidizes proteins or lipids, leading to bacteria death. To elucidate the oxidative processes that occur during killing of bacteria, Staphylococcus aureus was incubated with a standard photosensitizer, and the generation and decay of singlet oxygen was detected directly by its luminescence at 1,270 nm. At low bacterial concentrations, the time-resolved luminescence of singlet oxygen showed a decay time of 6 ؎ 2 s, which is an intermediate time for singlet oxygen decay in phospholipids of membranes (14 ؎ 2 s) and in the surrounding water (3.5 ؎ 0.5 s). Obviously, at low bacterial concentrations, singlet oxygen had sufficient access to water outside of S. aureus by diffusion. Thus, singlet oxygen seems to be generated in the outer cell wall areas or in adjacent cytoplasmic membranes of S. aureus. In addition, the detection of singlet oxygen luminescence can be used as a sensor of intracellular oxygen concentration. When singlet oxygen luminescence was measured at higher bacterial concentrations, the decay time increased significantly, up to Ϸ40 s, because of oxygen depletion at these concentrations. This observation is an important indicator that oxygen supply is a crucial factor in the efficacy of photodynamic inactivation of bacteria, and will be of particular significance should this approach be used against multiresistant bacteria.luminescence ͉ oxygen depletion ͉ Staphylococcus aureus

show abstract

“…Many lines of evidence have linked the oxidative damage generated by these species with the development of pathological conditions, such as atherosclerosis, neurodegenerative diseases, and cancer [1]. Singlet molecular oxygen [O 2 ( 1 ⌬ g )] is a reactive form of oxygen that can be produced by the action of peroxidases [2,3], UVA light in the presence of a sensitizer [4,5] and also during the dimerization reactions of peroxyl radicals in lipid peroxidation [6,7]. Electron-rich biomolecules, such as lipids, proteins, and DNA, can be important targets for O 2 ( 1 ⌬ g ) oxidation [8].…”

mentioning

confidence: 99%

Characterization of O₂ (¹Δ_g)-derived oxidation products of tryptophan: A combination of tandem mass spectrometry analyses and isotopic labeling studies

Ronsein

Oliveira

Medeiros

et al. 2009

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

The fragmentation mechanisms of singlet oxygen [O 2 ( 1 ⌬ g )]-derived oxidation products of tryptophan (W) were analyzed using collision-induced dissociation coupled with 18 O-isotopic labeling experiments and accurate mass measurements. The five identified oxidized products, namely two isomeric alcohols (trans and cis WOH), two isomeric hydroperoxides (trans and cis WOOH), and N-formylkynurenine (FMK), were shown to share some common fragment ions and losses of small neutral molecules. Conversely, each oxidation product has its own fragmentation mechanism and intermediates, which were confirmed by 18 O-labeling studies. Isomeric WOH lost mainly H 2 O ϩ CO, while WOOH showed preferential elimination of C 2 H 5 NO 3 by two distinct mechanisms. Differences in the spatial arrangement of the two isomeric WOHs led to differences in the intensities of the fragment ions. The same behavior was also found for trans and cis WOOH. FMK was shown to dissociate by a diverse range of mechanisms, with the loss of ammonia the most favored route. MS/MS analyses, 18 O-labeling, and H 2 18 O experiments demonstrated the ability of FMK to exchange its oxygen atoms with water. Moreover, this approach also revealed that the carbonyl group has more pronounced oxygen exchange ability compared with the formyl group. The understanding of fragmentation mechanisms involved in O 2 ( 1 ⌬ g )-mediated oxidation of W provides a useful step toward the structural characterization of oxidized peptides and proteins. (J Am Soc Mass Spectrom 2009, 20, 188 -197)

show abstract

Singlet Oxygen Generation by UVA Light Exposure of Endogenous Photosensitizers

Cited by 295 publications

References 39 publications

Riboflavin activated by ultraviolet A1 irradiation induces oxidative DNA damage-mediated mutations inhibited by vitamin C

Riboflavin activated by ultraviolet A1 irradiation induces oxidative DNA damage-mediated mutations inhibited by vitamin C

The role of singlet oxygen and oxygen concentration in photodynamic inactivation of bacteria

Characterization of O₂ (¹Δ_g)-derived oxidation products of tryptophan: A combination of tandem mass spectrometry analyses and isotopic labeling studies

Contact Info

Product

Resources

About

Singlet Oxygen Generation by UVA Light Exposure of Endogenous Photosensitizers

Cited by 295 publications

References 39 publications

Riboflavin activated by ultraviolet A1 irradiation induces oxidative DNA damage-mediated mutations inhibited by vitamin C

Riboflavin activated by ultraviolet A1 irradiation induces oxidative DNA damage-mediated mutations inhibited by vitamin C

The role of singlet oxygen and oxygen concentration in photodynamic inactivation of bacteria

Characterization of O2 (1Δg)-derived oxidation products of tryptophan: A combination of tandem mass spectrometry analyses and isotopic labeling studies

Contact Info

Product

Resources

About

Characterization of O₂ (¹Δ_g)-derived oxidation products of tryptophan: A combination of tandem mass spectrometry analyses and isotopic labeling studies