Aliaksandr V Mikulich, Vitaly Yu Plavskii, Antonina I Tretyakova, Raman K Nahorny, Andrey N Sobchuk, Natalia V Dudchik, Olga A Emeliyanova, Anastasia I Zhabrouskaya, Ludmila G Plavskaya, Tatsiana S Ananich, Olga N Dudinova, Ihar A Leusenka, Sergey V Yakimchuk, Alexei D Svechko, Tran Quoc Tien, Quang Cong Tong, Thanh Phuong Nguyen
{"title":"Potential of using medicinal plant extracts as photosensitizers for antimicrobial photodynamic therapy.","authors":"Aliaksandr V Mikulich, Vitaly Yu Plavskii, Antonina I Tretyakova, Raman K Nahorny, Andrey N Sobchuk, Natalia V Dudchik, Olga A Emeliyanova, Anastasia I Zhabrouskaya, Ludmila G Plavskaya, Tatsiana S Ananich, Olga N Dudinova, Ihar A Leusenka, Sergey V Yakimchuk, Alexei D Svechko, Tran Quoc Tien, Quang Cong Tong, Thanh Phuong Nguyen","doi":"10.1111/php.13935","DOIUrl":"10.1111/php.13935","url":null,"abstract":"<p><p>Antimicrobial photodynamic therapy (APDT) is a promising approach to overcome antimicrobial resistance. However, for widespread implementation of this approach, approved photosensitizers are needed. In this study, we used commercially available preparations (Calendulae officinalis floridis extract, Chamomillae recutitae floridis extract, Achillea millefolii herbae extract; Hypericum perforatum extract; Eucalyptus viminalis folia extract) as photosensitizers for inactivation of gram-negative (Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria. Spectral-luminescent analysis has shown that the major chromophores are of chlorophyll (mainly chlorophyll a and b) and hypericin nature. The extracts are efficient generators of singlet oxygen with quantum yield (γ<sub>Δ</sub>) from 0.40 to 0.64 (reference compound, methylene blue with γ<sub>Δ</sub> = 0.52). In APDT assays, bacteria before irradiation were incubated with extracts for 30 min. After irradiation and 24 h of incubation, colony-forming units (CFU) were counted. Upon exposure of P. aeruginosa to radiation of 405 nm, 590 nm, and 660 nm at equal energy dose of 30 J/cm<sup>2</sup> (irradiance - 100 mW/cm<sup>2</sup>, exposure time - 5 min), the most pronounced effect is observed with blue light (>3 log<sub>10</sub> reduction); in case of S. aureus, the effect is approximately equivalent for light of indicated wavelengths and dose (>4 log<sub>10</sub> reduction).</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":" ","pages":"1833-1847"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effectiveness of lapatinib for enhancing 5-aminolevulinic acid-mediated protoporphyrin IX fluorescence and photodynamic therapy in human cancer cell lines with varied ABCG2 activities.","authors":"Richard Howley, Jordyn Olsen, Bin Chen","doi":"10.1111/php.13936","DOIUrl":"10.1111/php.13936","url":null,"abstract":"<p><p>5-Aminolevulinic acid (ALA) is a prodrug for protoporphyrin IX (PpIX)-mediated photodynamic therapy (PDT) and fluorescence-guided tumor surgery. We previously reported that lapatinib, a repurposed ABCG2 inhibitor, enhanced ALA-induced PpIX fluorescence and PDT by blocking ABCG2-mediated PpIX efflux. In the present study, we evaluated how the variation in ABCG2 activities/protein levels affected tumor cell response to the enhancement of PpIX/PDT by lapatinib and Ko143, an ABCG2 tool inhibitor. ABCG2 activities and protein levels were determined in a panel of human cancer cell lines. Effects of lapatinib and Ko143 on enhancing ALA-PpIX fluorescence and PDT were evaluated and correlated with tumor cell ABCG2 activities. We found that both lapatinib and Ko143 enhanced ALA-PpIX fluorescence and PDT in a dose-dependent manner, although lapatinib exhibited lower efficacy and potency than Ko143 in nearly all cancer cell lines. The EC<sub>50</sub> of ABCG2 inhibitors for enhancing ALA-PpIX and PDT had a positive correlation with tumor cell ABCG2 activities, indicating that tumor cell lines with lower ABCG2 activities were more sensitive to ABCG2 inhibitors for PpIX/PDT enhancement. Our results suggest that, for optimal therapeutic enhancement, the dose of ABCG2 inhibitors needs to be tailored based on the ABCG2 expression/activity in tumors.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":" ","pages":"1579-1589"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140111145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anurag Prajapati, Rajesh K Yadav, Rehana Shahin, Ravindra Shukla, Shaifali Mishra, Satyam Singh, Suman Yadav, Jin-OoK Baeg, Rajat Singhal, Navneet K Gupta, Mohd Sajid Ali, Krishna Kumar Yadav
{"title":"Synergistic effects of covalently coupled eosin-Y with B<sub>en</sub>-graphitic carbon nitride framework for improved photocatalytic activity in solar light-driven Biginelli product generation and NADH regeneration.","authors":"Anurag Prajapati, Rajesh K Yadav, Rehana Shahin, Ravindra Shukla, Shaifali Mishra, Satyam Singh, Suman Yadav, Jin-OoK Baeg, Rajat Singhal, Navneet K Gupta, Mohd Sajid Ali, Krishna Kumar Yadav","doi":"10.1111/php.13986","DOIUrl":"10.1111/php.13986","url":null,"abstract":"<p><p>Elevated global pollution level is the prime reason that contributes to the onset of various harmful health diseases. The products of Biginelli reaction are enormously used in the pharmaceutical industry as they have antiviral, antibacterial, and calcium channel modulation abilities. This work reports a novel eosin Y sensitized boron graphitic carbon nitride (EY-B<sub>en-</sub>g-C<sub>3</sub>N<sub>4</sub>) as a photocatalyst that efficiently produced 3,4-dihydropyrimidine-2-(1H)-one by the Biginelli reaction of benzaldehyde, urea, and methyl acetoacetate. The photocatalyst EY-B<sub>en-</sub>g-C<sub>3</sub>N<sub>4</sub> showed a successful generation of 3,4-dihydropyrimidine-2-(1H)-one (Biginelli product) in good yield via photocatalysis which is an eco-friendly method and has facile operational process. In addition to the production of Biginelli products, the photocatalyst also showed a remarkable NADH regeneration of 81.18%. The incorporation of g-C<sub>3</sub>N<sub>4</sub> with boron helps increase the surface area and the incorporation of eosin Y which is an inexpensive and non-toxic dye, and in B<sub>en</sub>-g-C<sub>3</sub>N<sub>4</sub>, enhanced the light-harvesting capacity of the photocatalyst. The production of 3,4-dihydropyrimidine-2-(1H)-one and NADH by the EY-B<sub>en</sub>-g-C<sub>3</sub>N<sub>4</sub> photocatalyst is attributed to the requisite band gap, high molar absorbance, low rate of charge recombination, and increased capacity of the photocatalyst to harvest solar light energy.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":" ","pages":"1773-1786"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of 980 nm photobiomodulation delivered by a handpiece with Gaussian vs. Flat-Top profiles on proliferation and differentiation of buccal fat pad stem cells.","authors":"Ali Homayouni, Maryam Rezaie Rad, Hamidreza Barikani, Nasim Chiniforush, Solmaz Akbari","doi":"10.1111/php.13929","DOIUrl":"10.1111/php.13929","url":null,"abstract":"<p><p>The aim of this study was to compare the effectiveness of the Gaussian and Flat-Top profiles in proliferation and differentiation of mesenchymal stem cell of buccal fat pad. Based on the timing schedule and type of laser handpieces, the cells were assigned to a control group with no radiation, and two irradiation test groups (980 nm) with Flat-Top (F) (power of 1.1 W, beam area of 1 cm<sup>2</sup>) and standard Gaussian (G) (power of 0.7 W, beam area of 0.5 cm<sup>2</sup>) handpieces. Each test group was divided into three subgroups, receiving one time (60 J/cm<sup>2</sup>), two times (120 J/cm<sup>2</sup>), and three times (180 J/cm<sup>2</sup>) irradiation. 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and Annexin V tests were performed. The Alizarin Red staining and polymerase chain reaction tests were done both at the beginning and the end of the first and second weeks. The degree of mineralization and expression of osteogenic markers, RUNX2, OCN, and OPN were evaluated. Based on the MTT and Annexin V test results, both test groups outperformed the control group in degrees of cell proliferation during the first day of laser irradiation (p < 0.05). After one and two times irradiation, the expression of osteogenic markers in the test groups was significantly higher than the control group. PBM with Flat-Top and Gaussian handpieces can enhance ossification and cell differentiation regardless of the type of handpieces.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":" ","pages":"1902-1911"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140094514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Shades of phototoxicity in fluorescent imaging agents (that are not supposed to be phototoxic).","authors":"Serah Essang, Alexander Greer","doi":"10.1111/php.13856","DOIUrl":"10.1111/php.13856","url":null,"abstract":"<p><p>This article is a highlight of the paper by Huang et al. in this issue of Photochemistry and Photobiology. It describes shades of phototoxicity in fluorescent imaging agents that are not intended to be phototoxic. Phototoxicity was assessed using a modified neutral red uptake (NRU) in vitro assay with mean photo-effects (MPE) for the fluorescent agents IRdye800, indocyanine green (ICG), proflavine, and methylene blue (MB), with comparisons to known phototoxic agents benzoporphyrin derivative (BPD) and rose bengal (RB). The experimental conditions were aimed to mimic clinical settings, using not only visible light, but also near-infrared light for insight to photosafety and deep tissue damage. Molecular mechanisms underlying the phototoxicities were not sought, but IRdye800 and ICG were mainly deemed to be safe, whereas proflavine and MB would require precautions since phototoxicity can overshadow their utility as fluorescent imaging agents.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":" ","pages":"1694-1697"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10580454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chanda Bhandari, Azophi Moffat, John Fakhry, Ashritha Malkoochi, Austin Nguyen, Brian Trinh, Kenneth Hoyt, Michael D Story, Tayyaba Hasan, Girgis Obaid
{"title":"A single photodynamic priming protocol augments delivery of ⍺-PD-L1 mAbs and induces immunogenic cell death in head and neck tumors.","authors":"Chanda Bhandari, Azophi Moffat, John Fakhry, Ashritha Malkoochi, Austin Nguyen, Brian Trinh, Kenneth Hoyt, Michael D Story, Tayyaba Hasan, Girgis Obaid","doi":"10.1111/php.13865","DOIUrl":"10.1111/php.13865","url":null,"abstract":"<p><p>Photodynamic priming (PDP) leverages the photobiological effects of subtherapeutic photodynamic therapy (PDT) regimens to modulate the tumor vasculature and stroma. PDP also sensitizes tumors to secondary therapies, such as immunotherapy by inducing a cascade of molecular events, including immunogenic cell death (ICD). We and others have shown that PDP improves the delivery of antibodies, among other theranostic agents. However, it is not known whether a single PDP protocol is capable of both inducing ICD in vivo and augmenting the delivery of immune checkpoint inhibitors. In this rapid communication, we show for the first time that a single PDP protocol using liposomal benzoporphyrin derivative (Lipo-BPD, 0.25 mg/kg) with 690 nm light (75 J/cm<sup>2</sup>, 100 mW/cm<sup>2</sup>) simultaneously doubles the delivery of ⍺-PD-L1 antibodies in murine AT-84 head and neck tumors and induces ICD in vivo. ICD was observed as a 3-11 fold increase in tumor cell exposure of damage-associated molecular patterns (Calreticulin, HMGB1, and HSP70). These findings suggest that this single, highly translatable PDP protocol using clinically relevant Lipo-BPD holds potential for improving immunotherapy outcomes in head and neck cancer. It can do so by simultaneously overcoming physical barriers to the delivery of immune checkpoint inhibitors, and biochemical barriers that contribute to immunosuppression.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":" ","pages":"1647-1658"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41208987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shruti Vig, Brandon Gaitan, Lucas Frankle, Yu Chen, Rosalie Elespuru, T Joshua Pfefer, Huang-Chiao Huang
{"title":"Test method for evaluating the photocytotoxic potential of fluorescence imaging products.","authors":"Shruti Vig, Brandon Gaitan, Lucas Frankle, Yu Chen, Rosalie Elespuru, T Joshua Pfefer, Huang-Chiao Huang","doi":"10.1111/php.13836","DOIUrl":"10.1111/php.13836","url":null,"abstract":"<p><p>Various fluorescence imaging agents are currently under clinical studies. Despite significant benefits, phototoxicity is a barrier to the clinical translation of fluorophores. Current regulatory guidelines on medication-based phototoxicity focus on skin effects during sun exposure. However, with systemic and local administration of fluorophores and targeted illumination, there is now possibility of photochemical damage to deeper tissues during intraoperative imaging procedures. Hence, independent knowledge regarding phototoxicity is required to facilitate the development of fluorescence imaging products. Previously, we studied a cell-free assay for initial screening of reactive molecular species generation from fluorophores. The current work addresses a safety test method based on cell viability as an adjunct and a comparator with the cell-free assay. Our goal is to modify and implement an approach based on the in vitro 3T3 neutral red uptake assay of the Organization for Economic Co-Operation and Development Test Guideline 432 (OECD TG432) to evaluate the photocytotoxicity of clinically relevant fluorophores. These included indocyanine green (ICG), proflavine, methylene blue (MB), and IRDye800, as well as control photosensitizers, benzoporphyrin derivative (BPD) and rose bengal (RB). We performed measurements at agent concentrations and illumination parameters used for clinic imaging. Our results aligned with prior studies, indicating photocytotoxicity in RB and BPD and an absence of reactivity for ICG and IRDye800. DNA interactive agents, proflavine and MB, exhibited drug/light dose-response curves like photosensitizers. This study provides evidence and insights into practices useful for testing the photochemical safety of fluorescence imaging products.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":" ","pages":"1561-1578"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9931094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kazi Md Mahabubur Rahman, Barbara A Foster, Youngjae You
{"title":"Preclinical evaluation of singlet oxygen-cleavable prodrugs in combination with protoporphyrin IX-photodynamic therapy in an orthotopic rat model of non-muscle-invasive bladder cancer.","authors":"Kazi Md Mahabubur Rahman, Barbara A Foster, Youngjae You","doi":"10.1111/php.13838","DOIUrl":"10.1111/php.13838","url":null,"abstract":"<p><p>Photodynamic therapy (PDT) initially employed red light, which caused some patients to experience permanent bladder contractions. PDT using the FDA-approved drug hexaminolevulinate (HAL), which produces protoporphyrin IX (PpIX) in the tumor, showed some promise but has low efficacy in treating non-muscle-invasive bladder cancer (NMIBC). We developed singlet oxygen-activatable prodrugs of two anticancer drugs, paclitaxel and mitomycin C, to enhance the antitumor effect of PpIX-PDT without producing systemic side effects, by promoting only local release of the active chemotherapeutic agent. Orthotopic NMIBC model was used to compare the efficacy of prodrugs only, PpIX-PDT, and prodrugs + PpIX-PDT. 532 nm laser with a total power of 50 mW for 20 min (60 J, single treatment) was used with HAL and prodrugs. Histology and microscopic methods with image analysis were used to evaluate the tumor staging, antitumor efficacy, and local toxicity. Prodrug + PpIX-PDT produced superior antitumor efficacy than PpIX-PDT alone with statistical significance. Both PpIX-PDT alone and combination therapy resulted in mild damage to the bladder epithelium in the normal bladder area with no apparent damage to the muscle layer. Overall, SO-cleavable prodrugs improved the antitumor efficacy of PpIX-PDT without causing severe and permanent damage to the bladder muscle layer.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":" ","pages":"1590-1602"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10195824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kazi Md Mahabubur Rahman, Soniya Kumbham, Ganesh Bist, Sukyung Woo, Barbara A Foster, Youngjae You
{"title":"Comparison of red and green light for treating non-muscle invasive bladder cancer in rats using singlet oxygen-cleavable prodrugs with PPIX-PDT.","authors":"Kazi Md Mahabubur Rahman, Soniya Kumbham, Ganesh Bist, Sukyung Woo, Barbara A Foster, Youngjae You","doi":"10.1111/php.13933","DOIUrl":"10.1111/php.13933","url":null,"abstract":"<p><p>It has been 30 years since Photofrin-PDT was approved for the treatment of bladder cancer in Canada. However, Photofrin-PDT failed to gain popularity due to bladder complications. The PDT with red light and IV-administered Photofrin could permanently damage the bladder muscle. We have been developing a new combination strategy of PpIX-PDT with singlet oxygen-cleavable prodrugs for NMIBC with minimal side effects, avoiding damage to the bladder muscle layer. PpIX can be excited by either green (532 nm) or red (635 nm) light. Red light could be more efficacious in vivo due to its deeper tissue penetration than green light. Since HAL preferentially produces PpIX in tumors, we hypothesized that illuminating PpIX with red light might spare the muscle layer. PpIX-PDT was used to compare green and red laser efficacy in vitro and in vivo. The IC<sub>50</sub> of in vitro PpIX-PDT was 18 mW/cm<sup>2</sup> with the red laser and 22 mW/cm<sup>2</sup> with the green laser. The in vivo efficacy of the red laser with 50, 75, and 100 mW total dose was similar to the same dose of green laser in reducing tumor volume. Combining PpIX-PDT with prodrugs methyl-linked mitomycin C (Mt-L-MMC) and rhodamine-linked SN-38 (Rh-L-SN-38) significantly improved efficacy (tumor volume comparison). PpIX-PDT or PpIX-PDT + prodrug combination did not cause muscle damage in histological analysis. Overall, a combination of PpIX-PDT and prodrug with 635 nm laser is promising for non-muscle invasive bladder cancer treatment.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":" ","pages":"1659-1675"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140294238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"On the chemistry of sunlight-induced DNA lesions: A perspective on the alkaline chemical-induced reactivities of photo-damaged pyrimidine intra-strand dimers.","authors":"Ritu Chaturvedi, Eric C Long","doi":"10.1111/php.14031","DOIUrl":"10.1111/php.14031","url":null,"abstract":"<p><p>Photoexcitation of cellular as well as isolated DNAs upon exposure to the UV portion of sunlight or other UV sources can lead to the covalent dimerization of adjacent intra-strand stacked pyrimidine nucleobase rings (i.e., at 5'-Py-p-Py-3' sites). These modifications generate, in mammalian DNA as well as the DNA of all other forms of life, lesions such as cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs); and, in bacterial endospores, spore photoproducts (SPs). Importantly, the lesions formed in higher organisms can lead to disease states including cancer. While the formation, structure, and biological outcomes of pyrimidine dimer lesions have been the focus of much research, less has been known about their fundamental chemical properties until recently. Such an understanding of these lesions may lead to novel means to chemically identify and quantitate their presence in the genome. This review is intended to provide an overview of intra-strand pyrimidine dimer lesions derived from 5'-T-p-T sites with a focus on presenting what is currently known about their individual in vitro alkaline chemical reactivities. Included here are descriptions of investigations of the DNA lesions CPD, 6-4PP, and SP, and, for comparison, the monomeric pyrimidine lesion 5,6-dihydo-2'-deoxyuridine (dHdU). Of interest, the alkaline hydrolyses of these various lesions are all found to be centered on the loss of aromaticity of a lesion Py ring (T) leading to a carbonyl \"hot spot,\" the focal point of initial hydrolytic attack.</p>","PeriodicalId":20133,"journal":{"name":"Photochemistry and Photobiology","volume":" ","pages":"1698-1712"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}