Causal effects of genetically determined metabolites and metabolite ratios on esophageal diseases: a two-sample Mendelian randomization study.

BACKGROUND: Esophageal diseases (ED) are a kind of common diseases of upper digestive tract. Previous studies have proved that metabolic disorders are closely related to the occurrence and development of ED. However, there is a lack of evidence for causal relationships between metabolites and ED, as well as between metabolite ratios representing enzyme activities and ED. Herein, we explored the causality of genetically determined metabolites (GDMs) on ED through Mendelian Randomization (MR) study. METHODS: Two-sample Mendelian randomization analysis was used to assess the causal effects of genetically determined metabolites and metabolite ratios on ED. A genome-wide association analysis (GWAS) encompassing 850 individual metabolites along with 309 metabolite ratios served as the exposures. Meanwhile, the outcomes were defined by 10 types of ED phenotypes, including Congenital Malformations of Esophagus (CME), Esophageal Varices (EV), Esophageal Obstructions (EO), Esophageal Ulcers (EU), Esophageal Perforations (EP), Gastroesophageal Reflux Disease (GERD), Esophagitis, Barrett's Esophagus (BE), Benign Esophageal Tumors (BETs), and Malignant Esophageal Neoplasms (MENs). The standard inverse variance weighted (IVW) method was applied to estimate the causal relationship between exposure and outcome. Sensitivity analyses were carried out using multiple methods, including MR-Egger, Weighted Median, MR-PRESSO, Cochran's Q test, and leave-one-out analysis. P < 0.05 was conventionally considered statistically significant. After applying the Bonferroni correction for multiple testing, a threshold of P < 4.3E-05 (0.05/1159) was regarded as indicative of a statistically significant causal relationship. Furthermore, metabolic pathway analysis was performed using the web-based MetaboAnalyst 6.0 software. RESULTS: The findings revealed that initially, a total of 869 candidate causal association pairs ( P ivw < 0.05) were identified, involving 442 metabolites, 145 metabolite ratios and 10 types of ED. However, upon applying the Bonferroni correction for multiple testing, only 36 pairs remained significant, involving 28 metabolites (predominantly lipids and amino acids), 5 metabolite ratios and 6 types of ED. Sensitivity analyses and reverse MR were performed for these 36 causal association pairs, where the results showed that the pair of EV and 1-(1-enyl-palmitoyl)-2-linoleoyl-GPE (p-16:0/18:2) did not withstand the sensitivity tests, and Hexadecenedioate (C16:1-DC) was found to have a reverse causality with GERD. The final 34 robust causal pairs included 26 metabolites, 5 metabolite ratios and 5 types of ED. The involved 26 metabolites predominantly consisted of methylated nucleotides, glycine derivatives, sex hormones, phospholipids, bile acids, fatty acid dicarboxylic acid derivatives, and N-acetylated amino acids. Furthermore, through metabolic pathway analysis, we uncovered 8 significant pathways that played pivotal roles in five types of ED conditions. CONCLUSIONS: This study integrated genomics with metabolomics to assess causal relationships between ED and both metabolites and metabolite ratios, uncovering several key metabolic features in ED pathogenesis. These findings have potential as novel biomarkers for ED and provide insights into the disease's etiology and progression. However, further clinical and experimental validations are necessary.

1-Formyl-7-hydroxy-6,7-dihydro-5H-pyrrolizine (1-CHO-DHP)-Cysteine Conjugates: Metabolic Formation and Binding to Cellular DNA.

1-Formyl-7-hydroxy-6,7-dihydro-5H-pyrrolizine (1-CHO-DHP) is a potential proximate carcinogenic metabolite of pyrrolizidine alkaloids. In the present study, we determined that the reaction of 1-CHO-DHP with cysteine generated four identified products. By mass and 1H NMR spectral analyses, these products are cysteinyl-[2'-S-7]-1-CHO-DHP (P2), cysteinyl-[3'-N-7]-1-CHO-DHP (P3), 7-keto-DHP (P4), and 1-cysteinylimino-DHP (P5). These four compounds were also formed from the incubation of 1-CHO-DHP in HepG2 cells. Compounds P3 and P5 were interconvertible in acetonitrile and water. Incubation of P2 in HepG2 cells generated the four DHP-dG and -dA adducts that we propose to be potential common biomarkers of pyrrolizidine alkaloids exposure and pyrrolizidine alkaloids-induced liver tumor initiation. These four DHP-DNA adducts were also formed from the incubation of a mixture of P3 and P5 in HepG2 cells but not from the incubation with 7-keto-DHP. From the reaction of 1-CHO-DHP with glutathione, only trace amounts of the glutathione-1-CHO-DHP adduct were detected, with the structure unable to be characterized.

Pyrrolizidine Alkaloid-Protein Adducts: Potential Non-invasive Biomarkers of Pyrrolizidine Alkaloid-Induced Liver Toxicity and Exposure.

Pyrrolizidine alkaloids (PAs) are phytochemicals present in hundreds of plant species from different families widely distributed in many geographical regions around the world. PA-containing plants are probably the most common type of poisonous plants affecting livestock, wildlife, and humans. There have been many large-scale human poisonings caused by the consumption of food contaminated with toxic PAs. PAs require metabolic activation to generate pyrrolic metabolites to exert their toxicity. In this study, we developed a novel method to quantify pyrrole-protein adducts present in the blood. This method involves the use of AgNO3 in acidic ethanol to cleave the thiol linkage of pyrrole-protein (DHP-protein) adducts, and the resulting 7,9-di-C2H5O-DHP is quantified by HPLC-ES-MS/MS multiple reaction monitoring analysis in the presence of a known quantity of isotopically labeled 7,9-di-C2D5O-DHP internal standard. Using this method, we determined that diester-type PAs administered to rats produced higher levels of DHP-protein adducts than other types of PAs. The results suggest that DHP-protein adducts can potentially serve as minimally invasive biomarkers of PA exposure.

Reaction of dehydropyrrolizidine alkaloids with valine and hemoglobin.

Pyrrolizidine alkaloid-containing plants are probably the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids exert toxicity through metabolism to dehydropyrrolizidine alkaloids that bind to cellular protein and DNA, leading to hepatotoxicity, genotoxicity, and tumorigenicity. To date, it is not clear how dehydropyrrolizidine alkaloids bind to cellular constituents, including amino acids and proteins, resulting in toxicity. Metabolism of carcinogenic monocrotaline, riddelliine, and heliotrine produces dehydromonocrotaline, dehyroriddelliine, and dehydroheliotrine, respectively, as primary reactive metabolites. In this study, we report that reaction of dehydromonocrotaline with valine generated four highly unstable 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived valine (DHP-valine) adducts. For structural elucidation, DHP-valine adducts were derivatized with phenyl isothiocyanate (PITC) to DHP-valine-PITC products. After HPLC separation, their structures were characterized by mass spectrometry, UV-visible spectrophotometry, (1)H NMR, and (1)H-(1)H COSY NMR spectral analysis. Two DHP-valine-PITC adducts, designated as DHP-valine-PITC-1 and DHP-valine-PITC-3, had the amino group of valine linked to the C7 position of the necine base, and the other two DHP-valine-PITC products, DHP-valine-PITC-2 and DHP-valine-PITC-4, linked to the C9 position of the necine base. DHP-valine-PITC-1 was interconvertible with DHP-valine-PITC-3, and DHP-valine-PITC-2 was interconvertible with DHP-valine-PITC-4. Reaction of dehydroriddelliine and dehydroheliotrine with valine provided similar results. However, reaction of valine and dehydroretronecine (DHR) under similar experimental conditions did not produce DHP-valine adducts. Reaction of dehydromonocrotaline with rat hemoglobin followed by derivatization with PITC also generated the same four DHP-valine-PITC adducts. This represents the first full structural elucidation of protein conjugated pyrrolic adducts formed from reaction of dehydropyrrolizidine alkaloids with an amino acid (valine). In addition, it was found that DHP-valine-2 and DHP-valine-4, with the valine amino group linked at the C7 position of the necine base, can lose the valine moiety to form DHP.

Metabolic activation of pyrrolizidine alkaloids leading to phototoxicity and photogenotoxicity in human HaCaT keratinocytes.

Pyrrolizidine alkaloids, produced by a large number of poisonous plants with wide global distribution, are associated with genotoxicity, tumorigenicity, and hepatotoxicity in animals and humans. Mammalian metabolism converts pyrrolizidine alkaloids to reactive pyrrolic metabolites (dehydropyrrolizidine alkaloids) that form covalent protein and DNA adducts. Although a mechanistic understanding is currently unclear, pyrrolizidine alkaloids can cause secondary (hepatogenous) photosensitization and induce skin cancer. In this study, the phototoxicity of monocrotaline, riddelliine, dehydromonocrotaline, dehydroriddelliine, and dehydroretronecine (DHR) in human HaCaT keratinocytes under ultraviolet A (UVA) irradiation was determined. UVA irradiation of HaCaT cells treated with dehydromonocrotaline, dehydroriddelline, and DHR resulted in increased release of lactate dehydrogenase and enhanced photocytotoxicity proportional to the UVA doses. UVA-induced photochemical DNA damage also increased proportionally with dehydromonocrotaline and dehydroriddelline. UVA treatment potentiated the formation of 8-hydroxy-2'-deoxyguanosine DNA adducts induced by dehydromonocrotaline in HaCaT skin keratinocytes. Using electron spin resistance trapping, we found that UVA irradiation of dehydromonocrotaline and dehydroriddelliine generates reactive oxygen species (ROS), including hydroxyl radical, singlet oxygen, and superoxide, and electron transfer reactions, indicating that cytotoxicity and genotoxicity of these compounds could be mediated by ROS. Our results suggest that dehydropyrrolizidine alkaloids formed or delivered to the skin cause pyrrolizidine alkaloid-induced secondary photosensitization and possible skin cancer.

Advancements in DNA computing: exploring DNA logic systems and their biomedical applications.

DNA computing is regarded as one of the most promising candidates for the next generation of molecular computers, utilizing DNA to execute Boolean logic operations. In recent decades, DNA computing has garnered widespread attention due to its powerful programmable and parallel computing capabilities, demonstrating significant potential in intelligent biological analysis. This review summarizes the latest advancements in DNA logic systems and their biomedical applications. Firstly, it introduces recent DNA logic systems based on various materials such as functional DNA sequences, nanomaterials, and three-dimensional DNA nanostructures. The material innovations driving DNA computing have been summarized, highlighting novel molecular reactions and analytical performance metrics like efficiency, sensitivity, and selectivity. Subsequently, it outlines the biomedical applications of DNA computing-based multi-biomarker analysis in cellular imaging, clinical diagnosis, and disease treatment. Additionally, it discusses the existing challenges and future research directions for the development of DNA computing.

Pyrrolizidine alkaloid-derived DNA adducts as a common biological biomarker of pyrrolizidine alkaloid-induced tumorigenicity.

Pyrrolizidine alkaloid-containing plants are the most common poisonous plants affecting livestock, wildlife, and humans. The U.S. National Toxicology Program (NTP) classified riddelliine, a tumorigenic pyrrolizidine alkaloid, as "reasonably anticipated to be a human carcinogen" in the NTP 12th Report on Carcinogens in 2011. We previously determined that four DNA adducts were formed in rats dosed with riddelliine. The structures of the four DNA adducts were elucidated as (i) a pair of epimers of 7-hydroxy-9-(deoxyguanosin-N(2)-yl)dehydrosupinidine adducts (termed as DHP-dG-3 and DHP-dG-4) as the predominant adducts; and (ii) a pair of epimers of 7-hydroxy-9-(deoxyadenosin-N(6)-yl)dehydrosupinidine adducts (termed as DHP-dA-3 and DHP-dA-4 adducts). In this study, we selected a nontumorigenic pyrrolizidine alkaloid, platyphylliine, a pyrrolizidine alkaloid N-oxide, riddelliine N-oxide, and nine tumorigenic pyrrolizidine alkaloids (riddelliine, retrorsine, monocrotaline, lycopsamine, retronecine, lasiocarpine, heliotrine, clivorine, and senkirkine) for study in animals. Seven of the nine tumorigenic pyrrolizidine alkaloids, with the exception of lycopsamine and retronecine, are liver carcinogens. At 8-10 weeks of age, female F344 rats were orally gavaged for 3 consecutive days with 4.5 and 24 µmol/kg body weight test article in 0.5 mL of 10% DMSO in water. Twenty-four hours after the last dose, the rats were sacrificed, livers were removed, and liver DNA was isolated for DNA adduct analysis. DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4 adducts were formed in the liver of rats treated with the individual seven hepatocarcinogenic pyrrolizidine alkaloids and riddelliine N-oxide. These DNA adducts were not formed in the liver of rats administered retronecine, the nontumorigenic pyrrolizidine alkaloid, platyphylliine, or vehicle control. These results indicate that this set of DNA adducts, DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4, is a common biological biomarker of pyrrolizidine alkaloid-induced liver tumor formation. To date, this is the first finding that a set of exogenous DNA adducts are commonly formed from a series of tumorigenic xenobiotics.

Phototoxicity of herbal plants and herbal products.

Plants are used by humans in daily life in many different ways, including as food, herbal medicines, and cosmetics. Unfortunately, many natural plants and their chemical constituents are photocytotoxic and photogenotoxic, and these phototoxic phytochemicals are widely present in many different plant families. To date, information concerning the phototoxicity and photogenotoxicity of many plants and their chemical constituents is limited. In this review, we discuss phototoxic plants and their major phototoxic constituents; routes of human exposure; phototoxicity of these plants and their constituents; general mechanisms of phototoxicity of plants and phototoxic components; and several representative phototoxic plants and their photoactive chemical constituents.

Plasmonic alloys for quantitative determination and reaction monitoring of biothiols.

Biothiols participate in numerous physiological and pathological processes in an organism. Quantitative determination and reaction monitoring of biothiols have important implications for evaluating human health. Herein, we synthesized plasmonic alloys as the matrix to assist the laser desorption and ionization (LDI) process of biothiols in mass spectrometry (MS). Plasmonic alloys were constructed with mesoporous structures for LDI enhancement and trimetallic (PdPtAu) compositions for noble metal-thiol hybridization, toward enhanced detection sensitivity and selectivity, respectively. Plasmonic alloys enabled direct detection of biothiols from complex biosamples without any enrichment or separation. We introduced internal standards into the quantitative MS system, achieving accurate quantitation of methionine directly from serum samples with a recovery rate of 103.19% ± 6.52%. Moreover, we established a rapid monitoring platform for the oxidation-reduction reaction of glutathione, consuming trace samples down to 200 nL with an interval of seconds. This work contributes to the development of molecular tools based on plasmonic materials for biothiol detection toward real-case applications.

Full structure assignments of pyrrolizidine alkaloid DNA adducts and mechanism of tumor initiation.

Pyrrolizidine alkaloid-containing plants are widespread in the world and are probably the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids are among the first chemical carcinogens identified in plants. Previously, we determined that metabolism of pyrrolizidine alkaloids in vivo and in vitro generated a common set of DNA adducts that are responsible for tumor induction. Using LC-ESI/MS/MS analysis, we previously determined that four DNA adducts (DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4) were formed in rats dosed with riddelliine, a tumorigenic pyrrolizidine alkaloid. Because of the lack of an adequate amount of authentic standards, the structures of DHP-dA-3 and DHP-dA-4 were not elucidated, and the structural assignment for DHP-dG-4 warranted further validation. In this study, we developed an improved synthetic methodology for these DNA adducts, enabling their full structural elucidation by mass spectrometry and NMR spectroscopy. We determined that DHP-dA-3 and DHP-dA-4 are a pair of epimers of 7-hydroxy-9-(deoxyadenosin-N(6)-yl) dehydrosupinidine, while DHP-dG-4 is 7-hydroxy-9-(deoxyguanosin-N(2)-yl)dehydrosupinidine, an epimer of DHP-dG-3. With the structures of these DNA adducts unequivocally elucidated, we conclude that cellular DNA preferentially binds dehydropyrrolizidine alkaloid, for example, dehydroriddelliine, at the C9 position of the necine base, rather than at the C7 position. We also determined that DHP-dA-3 and DHP-dA-4, as well as DHP-dG-3 and DHP-dG-4, are interconvertible. This study represents the first report with detailed structural assignments of the DNA adducts that are responsible for pyrrolizidine alkaloid tumor induction on the molecular level. A mechanism of tumor initiation by pyrrolizidine alkaloids is consequently fully determined.

High-performance liquid chromatography electrospray ionization tandem mass spectrometry for the detection and quantitation of pyrrolizidine alkaloid-derived DNA adducts in vitro and in vivo.

Pyrrolizidine alkaloid-containing plants are widespread in the world and are probably the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids require metabolism to exert their genotoxicity and tumorigenicity. We have determined that the metabolism of a series of tumorigenic pyrrolizidine alkaloids in vitro or in vivo generates a common set of (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts that are responsible for tumor induction. The identification and quantitation of the DHP-derived DNA adducts formed in vivo and in vitro were accomplished previously by (32)P-postlabeling/HPLC methodology. In this article, we report the development of a sensitive and specific liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ES-MS/MS) method to detect DHP-derived DNA adducts formed in vitro and in vivo. The method is used to quantify the levels of DHP-2'-deoxyguanosine (dG) and DHP-2'-deoxyadenosine (dA) adducts by multiple reaction monitoring (MRM) analysis in the presence of known quantities of isotopically labeled DHP-dG and DHP-dA internal standards. This HPLC-ES-MS/MS method is accurate and precise. When applied to liver samples from rats treated with the pyrrolizidine alkaloids riddelliine and monocrotaline, the method provided significant new information regarding the mechanism of DNA adduct formation.

Photochemical formation of substituted pentacenes.

Substituted pentacenes (8a, 8b, 14a, and 14b) were prepared by Strating-Zwanenburg photodecarbonylation of diones (7a, 7b, 13a, and 13b). The compounds are red and stable in the solid state under inert atmosphere as well as in degassed solutions, but not in air. Each is soluble in common organic solvents where, unless protected, they are oxygen sensitive.

Probing connection of PBS with the photosystems in intact cells of Spirulina platensis by temperature-induced fluorescence fluctuation.

Temperature-dependent fluorescence for intact cells of cyanobacterium Spirulina platensis was detected to search for the connection of the phycobilisome (PBS) with Photosystem I (PSI) and Photosystem II (PSII). Some interesting results were obtained from the deconvoluted fluorescence components of C-phycocyanin (C-PC), allophycocyanin (APC), PSI and PSII as well as the fluorescence spectra of the intact cells at room temperature (RT=25 degrees C) and 0 degrees C. It was observed that, compared to those at RT, both of the fluorescence components for PSI and APC increased, whereas those for PSII and C-PC decreased at 0 degrees C with excitation at 580 nm, that is, the fluorescence for C-PC is not synchronous with that for APC, and the fluorescence fluctuation for PSI is not synchronous with that for PSII. On the other hand, the decrease in C-PC fluorescence is synchronous with the increase in PSI fluorescence, and the increase in APC fluorescence is synchronous with the decrease in PSII fluorescence. Therefore, it can be readily deduced that PBS should be coupled not only with PSII through the terminal acceptors in the APC core but also with PSI through C-PC in PBS rods at physiological condition, while at 0 degrees C, a migration of a PBS makes the APC partially detached from PSII but the C-PC more efficiently coupled with PSI. The results provide good evidences for "mobile PBS" model and "parallel connection" model but not for the "spillover" model.

Absolute configuration, stability, and interconversion of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine valine adducts and their phenylthiohydantoin derivatives.

Pyrrolizidine alkaloid-containing plants are widespread in the world and probably the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids require metabolic activation to form dehydropyrrolizidine alkaloids that bind to cellular proteins and DNA leading to hepatotoxicity, genotoxicity, and tumorigenicity. At present, it is not clear how dehydropyrrolizidine alkaloids bind to cellular amino acids and proteins to induced toxicity. We previously reported that reaction of dehydromonocrotaline with valine generated four highly unstable 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived valine (DHP-valine) adducts that upon reaction with phenyl isothiocyanate (PITC) formed four DHP-valine-PITC adduct isomers. In this study, we report the absolute configuration and stability of DHP-valine and DHP-valine-PITC adducts, and the mechanism of interconversion between DHP-valine-PITC adducts.

UVA photoirradiation of nitro-polycyclic aromatic hydrocarbons-induction of reactive oxygen species and formation of lipid peroxides.

Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are a class of genotoxic environmental contaminants. We have long been interested in determining the mechanisms by which nitro-PAHs induce genotoxicity. Although the metabolic activation of nitro-PAHs leading to toxicological activities has been well studied, the photo-induced activation of nitro-PAHs has seldom been reported. In this paper, we report photo-induced lipid peroxidation by 19 nitro-PAHs. The results indicated that all but two of the nitro-PAHs can induce lipid peroxidation. Mechanistic studies suggest that lipid peroxidation by nitro-PAHs is mediated by free radicals generated in the reaction. There was no structural correlation between the nitro-PAHs and their ability to induce lipid peroxidation upon UVA irradiation, or between the HOMO-LUMO gap and the ability to cause lipid peroxidation. Most of the nitro-PAHs are less potent in terms of causing lipid peroxidation than their parent PAHs. The lack of correlation is attributed to the complex photophysics and photochemistry of the nitro-PAHs and the yield of reactive oxygen species (ROS) and other factors.

Photoirradiation of polycyclic aromatic hydrocarbon diones by UVA light leading to lipid peroxidation.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous genotoxic environmental pollutants and potentially pose a health risk to humans. In most if not all cases, PAHs in the environment can be oxidized into their corresponding PAH-diones. This process is considered a detoxification pathway with regard to tumorigenicity. Nevertheless, photo-induced toxicological activity of PAH-diones has not been systematically investigated. In this study, we show that 27 potential environmental PAH-diones induced lipid peroxidation, in a dose (light) response manner, when irradiated with UVA at 7 and 21 J cm(-2). Photoirradiation in the presence of sodium azide, deuterated methanol, or superoxide dismutase revealed that lipid peroxidation is mediated by reactive oxygen species. Electron spin resonance (ESR) spin trapping studies supported this observation. These results suggest that UVA photoirradiation of PAH-diones generates reactive oxygen species and induces lipid peroxidation.

Photoirradiation of dehydropyrrolizidine alkaloids--formation of reactive oxygen species and induction of lipid peroxidation.

Pyrrolizidine alkaloid (PA)-containing plants are widespread in the world and are probably the most common poisonous plants affecting livestock, wildlife, and human. PAs require metabolic activation to generate pyrrolic metabolites (dehydro-PAs) that bind cellular protein and DNA, leading to hepatotoxicity and genotoxicity, including tumorigenicity. In this study we report that UVA photoirradiation of a series of dehydro-PAs, e.g., dehydromonocrotaline, dehydroriddelliine, dehydroretrorsine, dehydrosenecionine, dehydroseneciphylline, dehydrolasiocarpine, dehydroheliotrine, and dehydroretronecine (DHR) at 0-70 J/cm2 in the presence of a lipid, methyl linoleate, resulted in lipid peroxidation in a light dose-responsive manner. When irradiated in the presence of sodium azide, the level of lipid peroxidation decreased; lipid peroxidation was enhanced when methanol was replaced by deuterated methanol. These results suggest that singlet oxygen is a photo-induced product. When irradiated in the presence of superoxide dismutase, the level of lipid peroxidation decreased, indicating that lipid peroxidation is also mediated by superoxide. Electron spin resonance (ESR) spin trapping studies confirmed that both singlet oxygen and superoxide anion radical were formed during photoirradiation. These results indicate that UVA photoirradiation of dehydro-PAs generates reactive oxygen species (ROS) that mediated the initiation of lipid peroxidation. UVA irradiation of the parent PAs and other PA metabolites, including PA N-oxides, under similar experimental conditions did not produce lipid peroxidation. It is known that PAs induce skin cancer and are secondary (hepatogenous) photosensitization agents. Our results suggest that dehydro-PAs are the active metabolites responsible for skin cancer formation and PA-induced secondary photosensitization.

Photochemical synthesis of 2,3,9,10-tetrabromopentacene: its unusual photodimerization.

The photogeneration of 2,3,9,10-tetrabromopentacene from its precursor dione by photodecarbonylation was investigated. An unusual photodimer, 3,3',9,9',10,10'-hexabromo-2,2'-bipentacene, is produced.